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Venkatesan KB, Alamelu S, Srinivasan MK, Pachaiappan P. Nerolidol loaded beta cyclodextrin nanoparticles: a promising strategy for inducing apoptosis in breast cancer cells (MCF-7). JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2025:1-31. [PMID: 40326384 DOI: 10.1080/09205063.2025.2491605] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/12/2024] [Accepted: 04/02/2025] [Indexed: 05/07/2025]
Abstract
This study investigates the synthesis, characterization and anticancer efficacy of nerolidol-loaded beta cyclodextrin polymeric nanoparticles (NER-βCD-NPs) against MCF-7 breast cancer cells. Nerolidol, a sesquiterpene with anti-inflammatory, antioxidant, antimicrobial and anticancer properties, faces challenges of poor solubility and bioavailability, limiting its therapeutic potential. Breast cancer, a leading cause of cancer-related deaths in women, necessitates alternative therapies with fewer side effects compared to conventional chemotherapy. NER-βCD-NPs were synthesized and characterized using UV-visible spectroscopy, fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), dynamic light scattering (DLS), zeta potential analysis and differential scanning calorimetry (DSC). Drug encapsulation efficiency and in vitro release were analyzed using HPLC, while molecular docking assessed NER-βCD interactions. Characterization confirmed successful nanoparticle synthesis. UV-visible spectra and FTIR indicated encapsulation-specific changes, SEM revealed surface morphology, and DLS, zeta potential and DSC analyses demonstrated increased size and stability. The encapsulation efficiency was 84.9%, with 86% NER release at pH 5.4 over 48 h. Docking studies supported strong binding between NER and βCD (binding energy: -3.55 kcal/mol). Cytotoxicity assays showed significant MCF-7 cell inhibition. Mechanistic studies revealed reactive oxygen species (ROS) generation, mitochondrial dysfunction, nuclear changes and cell cycle arrest in the G0-G1 phase. Molecular analysis demonstrated apoptosis through upregulation of Bax, Caspase 6, Caspase 9 and Cytochrome c, alongside Bcl-2 downregulation. These results highlight NER-βCD-NPs as a promising strategy for breast cancer therapy, offering targeted delivery and enhanced therapeutic efficacy while mitigating nerolidol limitations. Further studies are warranted to validate their potential in clinical applications.
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Affiliation(s)
- Kamalesh Balakumar Venkatesan
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India
| | - Saravanan Alamelu
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India
| | - Manoj Kumar Srinivasan
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India
| | - Pugalendhi Pachaiappan
- Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar, Tamil Nadu, India
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Asl FSS, Malverdi N, Mojahedian F, Baziyar P, Nabi-Afjadi M. Discovery of effective GSK-3β inhibitors as therapeutic potential against Alzheimer's disease: A computational drug design insight. Int J Biol Macromol 2025; 306:141273. [PMID: 39978523 DOI: 10.1016/j.ijbiomac.2025.141273] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2024] [Revised: 12/30/2024] [Accepted: 02/17/2025] [Indexed: 02/22/2025]
Abstract
Alzheimer's disease (AD) is mostly thought to be caused by overactivity of glycogen synthase kinase 3-beta (GSK3-β). Therefore, a GSK-3β inhibitor may be a suggested medicine for Alzheimer's therapy. Nowadays, computational techniques are thought to be among the quickest and most affordable options for therapeutic design and drug discovery. Following a preliminary screening of flavonoids for possible protection against cognitive illnesses such as Alzheimer's, Amentoflavone, Curcumin, and Notopterol were shown to be promising candidates. Using molecular docking, the ligand orientation and binding energy in the ATP-binding pocket of GSK-3β were ascertained. Amentoflavone formed a hydrogen bond with the GSK-3β protein's ATP binding site during the molecular docking phase, obtaining the highest negative binding energy. However, when the results moved closer to a molecular dynamics simulation, the findings changed, and Curcumin was shown to be the most potent inhibitor. All structures remained stable during the MD simulation of the GSK-3β protein and its ligands. Moreover, compared to other natural compounds, Curcumin showed higher binding free energy. Therefore, Curcumin may be useful as a polyphenolic flavonoid in the prevention and treatment of AD. Hence, additional research in vitro and in vivo can focus on these flavonoid compounds as an alternative treatment.
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Affiliation(s)
| | - Nasrin Malverdi
- Department of Cell and Molecular Biology and Microbiology, Faculty of Biological Science and Technology, University of Isfahan, Isfahan, Iran
| | - Fatemeh Mojahedian
- Department of Biochemistry, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran
| | - Payam Baziyar
- Department of Molecular and Cell Biology, Faculty of Basic Sciences, University of Mazandaran, Babolsar, Iran.
| | - Mohsen Nabi-Afjadi
- Department of Biochemistry, Faculty of Biological Sciences, University of Tarbiat Modares, Tehran, Iran.
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3
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Ren J, Yan G, Yang L, Kong L, Guan Y, Sun H, Liu C, Liu L, Han Y, Wang X. Cancer chemoprevention: signaling pathways and strategic approaches. Signal Transduct Target Ther 2025; 10:113. [PMID: 40246868 PMCID: PMC12006474 DOI: 10.1038/s41392-025-02167-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2024] [Revised: 12/01/2024] [Accepted: 02/04/2025] [Indexed: 04/19/2025] Open
Abstract
Although cancer chemopreventive agents have been confirmed to effectively protect high-risk populations from cancer invasion or recurrence, only over ten drugs have been approved by the U.S. Food and Drug Administration. Therefore, screening potent cancer chemopreventive agents is crucial to reduce the constantly increasing incidence and mortality rate of cancer. Considering the lengthy prevention process, an ideal chemopreventive agent should be nontoxic, inexpensive, and oral. Natural compounds have become a natural treasure reservoir for cancer chemoprevention because of their superior ease of availability, cost-effectiveness, and safety. The benefits of natural compounds as chemopreventive agents in cancer prevention have been confirmed in various studies. In light of this, the present review is intended to fully delineate the entire scope of cancer chemoprevention, and primarily focuses on various aspects of cancer chemoprevention based on natural compounds, specifically focusing on the mechanism of action of natural compounds in cancer prevention, and discussing in detail how they exert cancer prevention effects by affecting classical signaling pathways, immune checkpoints, and gut microbiome. We also introduce novel cancer chemoprevention strategies and summarize the role of natural compounds in improving chemotherapy regimens. Furthermore, we describe strategies for discovering anticancer compounds with low abundance and high activity, revealing the broad prospects of natural compounds in drug discovery for cancer chemoprevention. Moreover, we associate cancer chemoprevention with precision medicine, and discuss the challenges encountered in cancer chemoprevention. Finally, we emphasize the transformative potential of natural compounds in advancing the field of cancer chemoprevention and their ability to introduce more effective and less toxic preventive options for oncology.
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Affiliation(s)
- Junling Ren
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Guangli Yan
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Le Yang
- State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou, China
| | - Ling Kong
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Yu Guan
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Hui Sun
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China.
| | - Chang Liu
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Lei Liu
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Ying Han
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China
| | - Xijun Wang
- State key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, National Chinmedomics Research Center, National TCM Key Laboratory of Serum Pharmacochemistry, Metabolomics Laboratory, Department of Pharmaceutical Analysis, Heilongjiang University of Chinese Medicine, Heping Road 24, Harbin, 150040, China.
- State Key Laboratory of Dampness Syndrome, The Second Affiliated Hospital Guangzhou University of Chinese Medicine, Dade Road 111, Guangzhou, China.
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Shadnoush M, Momenan M, Seidel V, Tierling S, Fatemi N, Nazemalhosseini-Mojarad E, Norooz MT, Cheraghpour M. A comprehensive update on the potential of curcumin to enhance chemosensitivity in colorectal cancer. Pharmacol Rep 2025; 77:103-123. [PMID: 39304638 DOI: 10.1007/s43440-024-00652-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2024] [Revised: 09/07/2024] [Accepted: 09/09/2024] [Indexed: 09/22/2024]
Abstract
Colorectal cancer (CRC) is one of the most common cancers and a major cause of cancer-related mortality worldwide. The efficacy of chemotherapy agents in CRC treatment is often limited due to toxic side effects, heterogeneity of cancer cells, and the possibility of chemoresistance which promotes cancer cell survival through several mechanisms. Combining chemotherapy agents with natural compounds like curcumin, a polyphenol compound from the Curcuma longa plant, has been reported to overcome chemoresistance and increase the sensitivity of cancer cells to chemotherapeutics. Curcumin, alone or in combination with chemotherapy agents, has been demonstrated to prevent chemoresistance by modulating various signaling pathways, reducing the expression of drug resistance-related genes. The purpose of this article is to provide a comprehensive update on studies that have investigated the ability of curcumin to enhance the efficacy of chemotherapy agents used in CRC. It is hoped that it can serve as a template for future research on the efficacy of curcumin, or other natural compounds, combined with chemotherapy agents to maximize the effectiveness of therapy and reduce the side effects that occur in CRC or other cancers.
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Affiliation(s)
- Mahdi Shadnoush
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O.Box, Tehran, 16635-148, Iran
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mehrnaz Momenan
- Department of Clinical Nutrition & Dietetics, Faculty of Nutrition Science and Food Technology, National Nutrition and Food Technology Research Institute, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Veronique Seidel
- Natural Products Research Laboratory, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK
| | - Sascha Tierling
- Department of Genetics/Epigenetics, Faculty NT, Life Sciences, Saarland University, Saarbrücken, Germany
| | - Nayeralsadat Fatemi
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O.Box, Tehran, 16635-148, Iran
| | - Ehsan Nazemalhosseini-Mojarad
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Tayefeh Norooz
- General Surgery Department, Modarres Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Makan Cheraghpour
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, P.O.Box, Tehran, 16635-148, Iran.
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Zheng G, Lin S, Wang S, Yan Y, Zheng D. Regulation of Natural Products on Wnt/β-Catenin Signaling Pathway in Diseases. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2025; 53:709-735. [PMID: 40374374 DOI: 10.1142/s0192415x25500272] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/17/2025]
Abstract
The Wnt/β-catenin signaling pathway plays a crucial role in both physiological and pathological conditions. Targeting molecules associated with the Wnt/β-catenin signaling pathway presents a promising approach for disease treatment. The use of natural products in treating various diseases is widespread due to their favorable biocompatibility, low toxicity, and high biological activity. Research has shown that natural products such as curcumin and resveratrol can regulate multiple signaling pathways under disease conditions, including the Wnt/β-catenin signaling pathway. However, the regulatory mechanisms of natural products remain incompletely understood. This review aims to explore the regulatory effects of natural products on the Wnt/β-catenin signaling pathway in certain diseases, especially in the process of tumor progression. It outlines the composition and mechanisms of the Wnt/β-catenin signaling pathway. Furthermore, we predicted the potential binding sites of these natural products to this pathway, summarized the effects of diverse natural products on this signaling pathway, and conducted a preliminary exploration ofd the mechanisms of the effects of natural products. In addition, we considered and discussed the limitations of natural products, such as potential side effects from long-term use and the precision in targeting the Wnt/β-catenin signaling pathway. This review provides a theoretical basis for the targeted strategy of the Wnt/β-catenin signaling pathway.
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Affiliation(s)
- Genggeng Zheng
- School of Stomatology, Fujian Medical University, Fuzhou, China
| | - Shuoqi Lin
- School of Stomatology, Fujian Medical University, Fuzhou, China
| | - Shijie Wang
- School of Stomatology, Fujian Medical University, Fuzhou, China
| | - Yuxiang Yan
- School of Stomatology, Fujian Medical University, Fuzhou, China
| | - Dali Zheng
- Fujian Key Laboratory of Oral Diseases, School and Hospital of Stomatology, Fujian Medical University, Fuzhou, China
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Xuan Y, Xu J, Que H, Zhu J. Effects of sulforaphane on prostate cancer stem cells-like properties: In vitro and molecular docking studies. Arch Biochem Biophys 2024; 762:110216. [PMID: 39549984 DOI: 10.1016/j.abb.2024.110216] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/22/2024] [Revised: 10/07/2024] [Accepted: 11/13/2024] [Indexed: 11/18/2024]
Abstract
The increasing incidence of prostate cancer worldwide has spurred research into novel therapeutics for its treatment and prevention. A critical factor contributing to its incidence and development is the presence of prostate cancer stem cells (PCSCs). Targeting PCSCs has become key in enhancing therapeutic and clinical outcomes of prostate cancer. Sulforaphane (SFN), a compound found in cruciferous vegetables, has shown effective antineoplastic activity in prostate cancer. Yet, its mechanisms of action in PCSCs remains unclear. In the present study, tumorsphere formation assay was used to isolate and enrich PCSCs from PC-3 cells. Our results found that SFN effectively reduced the activity of PCSCs, including the ability of tumorsphere formation, the number of CD133 positive cells, and the expression of PCSCs markers. Moreover, the data showed that SFN inhibited PCSCs through downregulating the activation of Wnt/β-catenin and hedgehog signaling pathways in PCSCs. Furthermore, the verification experiments showed that the activators of Wnt/β-catenin (LiCl) and hedgehog (purmorphamine) attenuated the effects of SFN on PCSCs, including the expression of stem cell markers, cell proliferation and apoptosis. Meanwhile, suppression of β-catenin or Smoothened enhanced the effects of SFN on PCSCs. In addition, molecular docking further indicated that SFN inhibited Wnt/β-catenin and hedgehog pathways by directly targeting β-catenin and Smoothened. Taken together, our results demonstrated that SFN targeted PCSCs through Wnt/β-catenin and hedgehog pathways to inhibit stemness and proliferation and induce apoptosis. Findings from this study could provide new insights into SFN as a dietary supplement or adjunct to chemotherapy.
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Affiliation(s)
- Yanling Xuan
- The First Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Jingyi Xu
- Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215008, China
| | - Hongliang Que
- Department of Urology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215008, China.
| | - Jianyun Zhu
- Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, 215008, China.
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Yao X, Yang Z, Hou G, Jiang J, Wang L, Jiang J. TRIM24/ZFX affects the stemness and resistance to 5-FU of colorectal cancer cells. J Chemother 2024:1-12. [PMID: 39221698 DOI: 10.1080/1120009x.2024.2376422] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2023] [Revised: 06/07/2024] [Accepted: 06/27/2024] [Indexed: 09/04/2024]
Abstract
Colorectal cancer (CRC) is the second leading cause of cancer death, and about 10% of all malignancies are CRC. Cancer stem cells are considered main culprits in CRC treatment resistance and disease recurrence. This study explored the effects of tripartite motif containing 24 (TRIM24) and zinc finger protein, X-linked (ZFX) on CRC cell stemness and 5-FU resistance. A 5-FU-resistant cell line (HT29-5-FU) was constructed for functional analysis of CRC 5-FU-resistant cells. qRT-PCR and western blot (WB) were employed to analyze mRNA and protein levels of ZFX in 5-FU resistant cells and sensitive cells. WB was also utilized to analyze the surface markers of stem cells in each group. CCK-8 assay determined the IC50 values of different cell groups treated with 5-FU. The sphere-forming ability of cells in each group was determined using tumor sphere assay. Dual-luciferase reporter gene assay validated binding of ZFX to TRIM24. ZFX was highly expressed in HT29-5-FU cells. Silencing ZFX significantly reduced the 5-FU resistance and IC50 value of HT29-5-FU cells, and the surface markers and cell sphere-forming ability of stem cells were also significantly reduced. The function of HT29 cells was opposite when ZFX was overexpressed. In CRC cells, TRIM24 was an upstream transcription factor of ZFX, and they interacted with each other. TRIM24 activated the expression of ZFX to influence the stemness and 5-FU resistance of cells. The TRIM24/ZFX regulatory axis affected the stemness of CRC cells and their sensitivity to 5-FU, providing potential drug targets for novel therapeutic avenues for CRC.
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Affiliation(s)
- Xuming Yao
- Department of Oncology, The Affliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, Zhejiang, China
| | - Zhiping Yang
- Department of Oncology, The Affliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, Zhejiang, China
| | - Guoxin Hou
- Department of Oncology, The Affliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, Zhejiang, China
| | - Jialu Jiang
- Department of Oncology, The Affliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, Zhejiang, China
| | - Lvbin Wang
- Department of Oncology, The Affliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, Zhejiang, China
| | - Jin Jiang
- Department of Oncology, The Affliated Hospital of Jiaxing University (The First Hospital of Jiaxing), Jiaxing, Zhejiang, China
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Guo S, Zheng S, Liu M, Wang G. Novel Anti-Cancer Stem Cell Compounds: A Comprehensive Review. Pharmaceutics 2024; 16:1024. [PMID: 39204369 PMCID: PMC11360402 DOI: 10.3390/pharmaceutics16081024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2024] [Revised: 07/24/2024] [Accepted: 07/26/2024] [Indexed: 09/04/2024] Open
Abstract
Cancer stem cells (CSCs) possess a significant ability to renew themselves, which gives them a strong capacity to form tumors and expand to encompass additional body areas. In addition, they possess inherent resistance to chemotherapy and radiation therapies used to treat many forms of cancer. Scientists have focused on investigating the signaling pathways that are highly linked to the ability of CSCs to renew themselves and maintain their stem cell properties. The pathways encompassed are Notch, Wnt/β-catenin, hedgehog, STAT3, NF-κB, PI-3K/Akt/mTOR, sirtuin, ALDH, MDM2, and ROS. Recent studies indicate that directing efforts towards CSC cells is essential in eradicating the overall cancer cell population and reducing the likelihood of tumor metastasis. As our comprehension of the mechanisms that stimulate CSC activity, growth, and resistance to chemotherapy advances, the discovery of therapeutic drugs specifically targeting CSCs, such as small-molecule compounds, holds the potential to revolutionize cancer therapy. This review article examines and analyzes the novel anti-CSC compounds that have demonstrated effective and selective targeting of pathways associated with the renewal and stemness of CSCs. We also discussed their special drug metabolism and absorption mechanisms. CSCs have been the subject of much study in cancer biology. As a possible treatment for malignancies, small-molecule drugs that target CSCs are gaining more and more attention. This article provides a comprehensive review of the current state of key small-molecule compounds, summarizes their recent developments, and anticipates the future discovery of even more potent and targeted compounds, opening up new avenues for cancer treatment.
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Affiliation(s)
- Shanchun Guo
- RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA;
| | - Shilong Zheng
- RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA;
| | - Mingli Liu
- Department of Biochemistry & Immunology, Morehouse School of Medicine, Atlanta, GA 30310, USA;
| | - Guangdi Wang
- RCMI Cancer Research Center and Department of Chemistry, Xavier University of Louisiana, New Orleans, LA 70125, USA;
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Abdel-Tawab MS, Fouad H, Sedeak AY, Doudar NA, Rateb EE, Faruk E, Reyad HR. Effects of mesenchymal stem cells versus curcumin on sonic hedgehog signaling in experimental model of Hepatocellular Carcinoma. Mol Biol Rep 2024; 51:740. [PMID: 38874802 DOI: 10.1007/s11033-024-09613-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2024] [Accepted: 05/03/2024] [Indexed: 06/15/2024]
Abstract
BACKGROUND Sonic Hedgehog (SHH) is a fundamental signaling pathway that controls tissue reconstruction, stem cell biology, and differentiation and has a role in gut tissue homeostasis and development. Dysregulation of SHH leads to the development of HCC. METHODS, AND RESULTS The present study was conducted to compare the effects of mesenchymal stem cells (MSCs) and curcumin on SHH molecular targets in an experimental model of HCC in rats. One hundred rats were divided equally into the following groups: control group, HCC group, HCC group received MSCs, HCC group received curcumin, and HCC group received MSCs and curcumin. Histopathological examinations were performed, and gene expression of SHH signaling target genes (SHH, PTCH1, SMOH, and GLI1) was assessed by real-time PCR in rat liver tissue. Results showed that SHH target genes were significantly upregulated in HCC-untreated rat groups and in MSC-treated groups, with no significant difference between them. Administration of curcumin with or without combined administration of MSCs led to a significant down-regulation of SHH target genes, with no significant differences between both groups. As regards the histopathological examination of liver tissues, both curcumin and MSCs, either through separate use or their combined use, led to a significant restoration of normal liver pathology. CONCLUSIONS In conclusion, SHH signaling is upregulated in the HCC experimental model. MSCs do not inhibit the upregulated SHH target genes in HCC. Curcumin use with or without MSCs administration led to a significant down-regulation of SHH signaling in HCC and a significant restoration of normal liver pathology.
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Affiliation(s)
- Marwa Sayed Abdel-Tawab
- Medical Biochemistry Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt.
| | - Hanan Fouad
- Medical Biochemistry Department, Faculty of Medicine, Cairo University, POB 12613, Cairo, Egypt
- Faculty of Medicine, Galala University, POB 43711, Attaka, Suez Governorate, Egypt
| | - Ahmed Yahia Sedeak
- Anatomy and Embryology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Noha A Doudar
- Clinical and Chemical Pathology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Enas Ezzat Rateb
- Physiology Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
| | - Eman Faruk
- Department of Anatomy, Faculty of Medicine, Umm Al-Qura University, Mecca, Saudi Arabia
- Department of Histology and Cytology, Faculty of Medicine, Benha University, Benha, Egypt
| | - Hoda Ramadan Reyad
- Medical Biochemistry Department, Faculty of Medicine, Beni-Suef University, Beni-Suef, Egypt
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Lv H, Qian D, Xu S, Fan G, Qian Q, Cha D, Qian X, Zhou G, Lu B. Modulation of long noncoding RNAs by polyphenols as a novel potential therapeutic approach in lung cancer: A comprehensive review. Phytother Res 2024; 38:3240-3267. [PMID: 38739454 DOI: 10.1002/ptr.8202] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/13/2023] [Revised: 03/10/2024] [Accepted: 03/19/2024] [Indexed: 05/16/2024]
Abstract
Lung cancer stands as a formidable global health challenge, necessitating innovative therapeutic strategies. Polyphenols, bioactive compounds synthesized by plants, have garnered attention for their diverse health benefits, particularly in combating various cancers, including lung cancer. The advent of whole-genome and transcriptome sequencing technologies has illuminated the pivotal roles of long noncoding RNAs (lncRNAs), operating at epigenetic, transcriptional, and posttranscriptional levels, in cancer progression. This review comprehensively explores the impact of polyphenols on both oncogenic and tumor-suppressive lncRNAs in lung cancer, elucidating on their intricate regulatory mechanisms. The comprehensive examination extends to the potential synergies when combining polyphenols with conventional treatments like chemotherapy, radiation, and immunotherapy. Recognizing the heterogeneity of lung cancer subtypes, the review emphasizes the need for the integration of nanotechnology for optimized polyphenol delivery and personalized therapeutic approaches. In conclusion, we collect the latest research, offering a holistic overview of the evolving landscape of polyphenol-mediated modulation of lncRNAs in lung cancer therapy. The integration of polyphenols and lncRNAs into multidimensional treatment strategies holds promise for enhancing therapeutic efficacy and navigating the challenges associated with lung cancer treatment.
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Affiliation(s)
- Hong Lv
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Dawei Qian
- Department of Thoracic Surgery, Tongling Yi'an District People's Hospital, Tongling, China
| | - Shuhua Xu
- Department of Cardiothoracic Surgery, Dongtai Hospital of Traditional Chinese Medicine, Dongtai, China
| | - Guiqin Fan
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Qiuhong Qian
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Dongsheng Cha
- Department of Thoracic Surgery, Tongling Yi'an District People's Hospital, Tongling, China
| | - Xingjia Qian
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
| | - Guoping Zhou
- Department of Cardiothoracic Surgery, Dongtai Hospital of Traditional Chinese Medicine, Dongtai, China
| | - Bing Lu
- Department of Pulmonary and Critical Care Medicine, Taicang TCM Hospital, Taicang, China
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Fatima F, Chourasiya NK, Mishra M, Kori S, Pathak S, Das R, Kashaw V, Iyer AK, Kashaw SK. Curcumin and its Derivatives Targeting Multiple Signaling Pathways to Elicit Anticancer Activity: A Comprehensive Perspective. Curr Med Chem 2024; 31:3668-3714. [PMID: 37221681 DOI: 10.2174/0929867330666230522144312] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2022] [Revised: 03/23/2023] [Accepted: 04/07/2023] [Indexed: 05/25/2023]
Abstract
The uncontrolled growth and spread of aberrant cells characterize the group of disorders known as cancer. According to GLOBOCAN 2022 analysis of cancer patients in either developed countries or developing countries the main concern cancers are breast cancer, lung cancer, and liver cancer which may rise eventually. Natural substances with dietary origins have gained interest for their low toxicity, anti-inflammatory, and antioxidant effects. The evaluation of dietary natural products as chemopreventive and therapeutic agents, the identification, characterization, and synthesis of their active components, as well as the enhancement of their delivery and bioavailability, have all received significant attention. Thus, the treatment strategy for concerning cancers must be significantly evaluated and may include the use of phytochemicals in daily lifestyle. In the present perspective, we discussed one of the potent phytochemicals, that has been used over the past few decades known as curcumin as a panacea drug of the "Cure-all" therapy concept. In our review firstly we included exhausted data from in vivo and in vitro studies on breast cancer, lung cancer, and liver cancer which act through various cancer-targeting pathways at the molecular level. Now, the second is the active constituent of turmeric known as curcumin and its derivatives are enlisted with their targeted protein in the molecular docking studies, which help the researchers design and synthesize new curcumin derivatives with respective implicated molecular and cellular activity. However, curcumin and its substituted derivatives still need to be investigated with unknown targeting mechanism studies in depth.
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Affiliation(s)
- Firdous Fatima
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Nikhil Kumar Chourasiya
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Mitali Mishra
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Shivam Kori
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Sandhya Pathak
- Department of Chemistry, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Ratnesh Das
- Department of Chemistry, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
| | - Varsha Kashaw
- Sagar Institute of Pharmaceutical Sciences, Sagar (M.P.), India
| | - Arun K Iyer
- Use-inspired Biomaterials & Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, Michigan, USA
- Molecular Imaging Program, Karmanos Cancer Institute, Detroit, Michigan, USA
| | - Sushil Kumar Kashaw
- Integrated Drug Discovery Research Laboratory, Department of Pharmaceutical Sciences, Dr. Harisingh Gour University (A Central University), Sagar (MP), India
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12
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Memarzia A, Saadat S, Asgharzadeh F, Behrouz S, Folkerts G, Boskabady MH. Therapeutic effects of medicinal plants and their constituents on lung cancer, in vitro, in vivo and clinical evidence. J Cell Mol Med 2023; 27:2841-2863. [PMID: 37697969 PMCID: PMC10538270 DOI: 10.1111/jcmm.17936] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2023] [Revised: 08/07/2023] [Accepted: 08/18/2023] [Indexed: 09/13/2023] Open
Abstract
The most common type of cancer in the world is lung cancer. Traditional treatments have an important role in cancer therapy. In the present review, the most recent findings on the effects of medicinal plants and their constituents or natural products (NP) in treating lung cancer are discussed. Empirical studies until the end of March 2022 were searched using the appropriate keywords through the databases PubMed, Science Direct and Scopus. The extracts and essential oils tested were all shown to effect lung cancer by several mechanisms including decreased tumour weight and volume, cell viability and modulation of cytokine. Some plant constituents increased expression of apoptotic proteins, the proportion of cells in the G2/M phase and subG0/G1 phase, and Cyt c levels. Also, natural products (NP) activate apoptotic pathways in lung cancer cell including p-JNK, Akt/mTOR, PI3/ AKT\ and Bax, Bcl2, but suppressed AXL phosphorylation. Plant-derived substances altered the cell morphology, reduced cell migration and metastasis, oxidative marker production, p-eIF2α and GRP78, IgG, IgM levels and reduced leukocyte counts, LDH, GGT, 5'NT and carcinoembryonic antigen (CEA). Therefore, medicinal plant extracts and their constituents could have promising therapeutic value for lung cancer, especially if used in combination with ordinary anti-cancer drugs.
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Affiliation(s)
- Arghavan Memarzia
- Applied Biomedical Research CenterMashhad University of Medical SciencesMashhadIran
- Department of Physiology, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
| | - Saeideh Saadat
- Applied Biomedical Research CenterMashhad University of Medical SciencesMashhadIran
- Department of Physiology, School of MedicineZahedan University of Medical SciencesZahedanIran
| | - Fereshteh Asgharzadeh
- Department of Physiology, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
| | - Sepide Behrouz
- Department of Animal Science, Faculty of AgricultureUniversity of BirjandBirjandIran
| | - Gert Folkerts
- Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Faculty of ScienceUtrecht UniversityUtrechtNetherlands
| | - Mohammad Hossein Boskabady
- Applied Biomedical Research CenterMashhad University of Medical SciencesMashhadIran
- Department of Physiology, Faculty of MedicineMashhad University of Medical SciencesMashhadIran
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13
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Shen X, Gao C, Li H, Liu C, Wang L, Li Y, Liu R, Sun C, Zhuang J. Natural compounds: Wnt pathway inhibitors with therapeutic potential in lung cancer. Front Pharmacol 2023; 14:1250893. [PMID: 37841927 PMCID: PMC10568034 DOI: 10.3389/fphar.2023.1250893] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2023] [Accepted: 09/20/2023] [Indexed: 10/17/2023] Open
Abstract
The Wnt/β-catenin pathway is abnormally activated in most lung cancer tissues and considered to be an accelerator of carcinogenesis and lung cancer progression, which is closely related to increased morbidity rates, malignant progression, and treatment resistance. Although targeting the canonical Wnt/β-catenin pathway shows significant potential for lung cancer therapy, it still faces challenges owing to its complexity, tumor heterogeneity and wide physiological activity. Therefore, it is necessary to elucidate the role of the abnormal activation of the Wnt/β-catenin pathway in lung cancer progression. Moreover, Wnt inhibitors used in lung cancer clinical trials are expected to break existing therapeutic patterns, although their adverse effects limit the treatment window. This is the first study to summarize the research progress on various compounds, including natural products and derivatives, that target the canonical Wnt pathway in lung cancer to develop safer and more targeted drugs or alternatives. Various natural products have been found to inhibit Wnt/β-catenin in various ways, such as through upstream and downstream intervention pathways, and have shown encouraging preclinical anti-tumor efficacy. Their diversity and low toxicity make them a popular research topic, laying the foundation for further combination therapies and drug development.
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Affiliation(s)
- Xuetong Shen
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Chundi Gao
- College of Traditional Chinese Medicine, Weifang Medical University, Weifang, China
| | - Huayao Li
- College of Traditional Chinese Medicine, Weifang Medical University, Weifang, China
| | - Cun Liu
- College of Traditional Chinese Medicine, Weifang Medical University, Weifang, China
| | - Longyun Wang
- State Key Laboratory of Quality Research in Chinese Medicine and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, China
| | - Ye Li
- State Key Laboratory of Quality Research in Chinese Medicine and Faculty of Chinese Medicine, Macau University of Science and Technology, Taipa, China
| | - Ruijuan Liu
- Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, China
| | - Changgang Sun
- College of Traditional Chinese Medicine, Weifang Medical University, Weifang, China
- Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, China
| | - Jing Zhuang
- Department of Oncology, Weifang Traditional Chinese Hospital, Weifang, China
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14
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Jing J, Wu Z, Wang J, Luo G, Lin H, Fan Y, Zhou C. Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies. Signal Transduct Target Ther 2023; 8:315. [PMID: 37596267 PMCID: PMC10439210 DOI: 10.1038/s41392-023-01559-5] [Citation(s) in RCA: 42] [Impact Index Per Article: 21.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/19/2023] [Accepted: 07/05/2023] [Indexed: 08/20/2023] Open
Abstract
The past decade has seen significant advances in our understanding of Hedgehog (HH) signaling pathway in various biological events. HH signaling pathway exerts its biological effects through a complex signaling cascade involved with primary cilium. HH signaling pathway has important functions in embryonic development and tissue homeostasis. It plays a central role in the regulation of the proliferation and differentiation of adult stem cells. Importantly, it has become increasingly clear that HH signaling pathway is associated with increased cancer prevalence, malignant progression, poor prognosis and even increased mortality. Understanding the integrative nature of HH signaling pathway has opened up the potential for new therapeutic targets for cancer. A variety of drugs have been developed, including small molecule inhibitors, natural compounds, and long non-coding RNA (LncRNA), some of which are approved for clinical use. This review outlines recent discoveries of HH signaling in tissue homeostasis and cancer and discusses how these advances are paving the way for the development of new biologically based therapies for cancer. Furthermore, we address status quo and limitations of targeted therapies of HH signaling pathway. Insights from this review will help readers understand the function of HH signaling in homeostasis and cancer, as well as opportunities and challenges of therapeutic targets for cancer.
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Affiliation(s)
- Junjun Jing
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Zhuoxuan Wu
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Jiahe Wang
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Guowen Luo
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Hengyi Lin
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China
| | - Yi Fan
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
- Department of Cariology and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
| | - Chenchen Zhou
- State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
- Department of Pediatric Dentistry, West China Hospital of Stomatology, Sichuan University, Chengdu, 610041, China.
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15
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Gui H, Chen X, Li L, Zhu L, Jing Q, Nie Y, Zhang X. Psychological distress influences lung cancer: Advances and perspectives on the immune system and immunotherapy. Int Immunopharmacol 2023; 121:110251. [PMID: 37348230 DOI: 10.1016/j.intimp.2023.110251] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2023] [Revised: 04/18/2023] [Accepted: 04/25/2023] [Indexed: 06/24/2023]
Abstract
Lung cancer has the highest incidence rate and mortality worldwide. Moreover, multiple factors may cause heterogeneity in the efficacy of immunotherapy for lung cancer, and preclinical studies have gradually uncovered the promotive effects of psychological distress (PD) on tumor hallmarks. Therefore, treatment targeted at PD may be a vital factor in adjusting and improving immunotherapy for lung cancer. Here, by focusing on the central nervous system, as well as stress-related crucial neurotransmitters and hormones, we highlight the effects of PD on the lung immune system, the lung tumor microenvironment (TME) and immunotherapy, which brings a practicable means and psychosocial perspective to lung cancer treatment.
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Affiliation(s)
- Huan Gui
- Department of Hyperbaric Oxygen, People`s Hospital of Qianxinan Buyi and Miao Minority Autonomous Prefecture, Xingyi 562400, China; School of Medicine, Guizhou University, Guiyang 550025, China
| | - Xulong Chen
- School of Medicine, Guizhou University, Guiyang 550025, China; Department of Urology, Affiliated Hospital of Guizhou Medical University, Guiyang 550004, China
| | - Linzhao Li
- School of Medicine, Guizhou University, Guiyang 550025, China
| | - Lan Zhu
- School of Medicine, Guizhou University, Guiyang 550025, China
| | - Qianyu Jing
- NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang 550002, China
| | - Yingjie Nie
- School of Medicine, Guizhou University, Guiyang 550025, China; NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang 550002, China.
| | - Xiangyan Zhang
- School of Medicine, Guizhou University, Guiyang 550025, China; NHC Key Laboratory of Pulmonary Immunological Diseases, Guizhou Provincial People's Hospital, Guiyang 550002, China.
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16
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Hassanizadeh S, Shojaei M, Bagherniya M, Orekhov AN, Sahebkar A. Effect of nano-curcumin on various diseases: A comprehensive review of clinical trials. Biofactors 2023. [PMID: 36607090 DOI: 10.1002/biof.1932] [Citation(s) in RCA: 30] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2022] [Accepted: 12/19/2022] [Indexed: 01/07/2023]
Abstract
The antioxidant, anti-inflammatory, and antibacterial properties of curcumin have made it a valuable herbal product for improving various disorders, such as COVID-19, cancer, depression, anxiety, osteoarthritis, migraine, and diabetes. Recent research has demonstrated that encapsulating curcumin in nanoparticles might improve its therapeutic effects and bioavailability. To our knowledge, the efficacy of nano-curcumin on different aspects of health and disease has not been summarized in a study. Therefore, this review aimed to evaluate nano-curcumin's efficacy in various diseases based on the findings of clinical trials. In order to review publications focusing on nanocurcumin's impact on various diseases, four databases were searched, including PubMed, Scopus, Web of Science, and Google Scholar. This review highlights the potential benefits of nano-curcumin in improving a wide range of human diseases including COVID-19, neurological disorders, chronic disease, oral diseases, osteoarthritis, metabolic syndrome, and other diseases, especially as an adjunct to standard therapy and a healthy lifestyle.
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Affiliation(s)
- Shirin Hassanizadeh
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mehrnaz Shojaei
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Mohammad Bagherniya
- Nutrition and Food Security Research Center and Department of Community Nutrition, School of Nutrition and Food Science, Isfahan University of Medical Sciences, Isfahan, Iran
- Anesthesia and Critical Care Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Alexander N Orekhov
- Institute of General Pathology and Pathophysiology, Moscow, Russia
- Institute for Atherosclerosis Research, Moscow, Russia
| | - Amirhossein Sahebkar
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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17
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Zhang T, Cao W, Sun H, Yu D, Zhong C. Diallyl Trisulfide Suppresses the Renal Cancer Stem-like Cell Properties via Nanog. Nutr Cancer 2023; 75:971-979. [PMID: 36562732 DOI: 10.1080/01635581.2022.2156553] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Cancer stem-like cells (CSCs), which play an important role in tumor initiation and progression, have been identified in many cancers. Diallyl trisulfide (DATS) is an organosulfur compound extracted from garlic with anticancer activities. Nanog is a transcription factor responsible for maintaining the stemness of CSCs, but its role in the DATS-induced attenuation of renal CSC properties is unknown. In this study, renal CSCs were enriched from human renal cancer cell lines 786-O and ACHN cultured in a serum-free medium (SFM). The properties of CSCs were analyzed by evaluating the ability of the cells in sphere formation and measuring the expression of stem cell markers. We found that downregulation of Nanog inhibited renal CSC properties. DATS suppressed renal CSC activities by reducing tumorsphere formation, decreasing stem cell markers including Nanog, CD44, ALDH1A1, and Oct4, inhibiting cell proliferation and promoting apoptosis. We further revealed that overexpression of Nanog reversed the suppressive effects of DATS on renal CSCs. Taken together, our results demonstrated that DATS inhibited renal CSCs by suppressing Nanog. These novel findings suggested that, through Nanog targeting, DATS can potentially be used as an anti-tumor agent for renal cancer.
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Affiliation(s)
- Taotao Zhang
- Health Management Center , The Second Affiliated Hospital of Anhui Medical University, Hefei, China.,Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Wanshuang Cao
- Cancer Research Division, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Hongliang Sun
- Department of Urology, Affiliated Taikang Xianlin Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China
| | - Dexin Yu
- Department of Urology, The Second Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Caiyun Zhong
- Cancer Research Division, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China
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18
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Lo Iacono M, Gaggianesi M, Bianca P, Brancato OR, Muratore G, Modica C, Roozafzay N, Shams K, Colarossi L, Colarossi C, Memeo L, Turdo A, Veschi V, Di Franco S, Todaro M, Stassi G. Destroying the Shield of Cancer Stem Cells: Natural Compounds as Promising Players in Cancer Therapy. J Clin Med 2022; 11:6996. [PMID: 36498571 PMCID: PMC9737492 DOI: 10.3390/jcm11236996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/21/2022] [Revised: 11/21/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
In a scenario where eco-sustainability and a reduction in chemotherapeutic drug waste are certainly a prerogative to safeguard the biosphere, the use of natural products (NPs) represents an alternative therapeutic approach to counteract cancer diseases. The presence of a heterogeneous cancer stem cell (CSC) population within a tumor bulk is related to disease recurrence and therapy resistance. For this reason, CSC targeting presents a promising strategy for hampering cancer recurrence. Increasing evidence shows that NPs can inhibit crucial signaling pathways involved in the maintenance of CSC stemness and sensitize CSCs to standard chemotherapeutic treatments. Moreover, their limited toxicity and low costs for large-scale production could accelerate the use of NPs in clinical settings. In this review, we will summarize the most relevant studies regarding the effects of NPs derived from major natural sources, e.g., food, botanical, and marine species, on CSCs, elucidating their use in pre-clinical and clinical studies.
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Affiliation(s)
- Melania Lo Iacono
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Miriam Gaggianesi
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Paola Bianca
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Ornella Roberta Brancato
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Giampaolo Muratore
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Chiara Modica
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Narges Roozafzay
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Kimiya Shams
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Lorenzo Colarossi
- Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, 95029 Catania, Italy
| | - Cristina Colarossi
- Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, 95029 Catania, Italy
| | - Lorenzo Memeo
- Department of Experimental Oncology, Mediterranean Institute of Oncology, Viagrande, 95029 Catania, Italy
| | - Alice Turdo
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Veronica Veschi
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Simone Di Franco
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
| | - Matilde Todaro
- Department of Health Promotion Sciences, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, 90127 Palermo, Italy
| | - Giorgio Stassi
- Department of Surgical, Oncological and Stomatological Sciences (DICHIRONS), University of Palermo, 90127 Palermo, Italy
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19
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Li P, Pu S, Lin C, He L, Zhao H, Yang C, Guo Z, Xu S, Zhou Z. Curcumin selectively induces colon cancer cell apoptosis and S cell cycle arrest by regulates Rb/E2F/p53 pathway. J Mol Struct 2022. [DOI: 10.1016/j.molstruc.2022.133180] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
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20
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Curcumin Induces Apoptosis of Chemoresistant Lung Cancer Cells via ROS-Regulated p38 MAPK Phosphorylation. Int J Mol Sci 2022; 23:ijms23158248. [PMID: 35897820 PMCID: PMC9367815 DOI: 10.3390/ijms23158248] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2022] [Revised: 07/22/2022] [Accepted: 07/23/2022] [Indexed: 02/01/2023] Open
Abstract
This study aimed to challenge chemoresistance by curcumin (CUR) with drug-selected human lung cancer A549 sublines that continuously proliferate in the present of docetaxel (DOC) and vincristine (VCR). Their sensitivities to CUR were measured by MTT assay and the particular intracellular reactive oxygen species (ROS) was detected by fluorescence activated cell sorting (FACS) analysis. Apoptosis was analyzed by Annexin V assay of the flow cytometry. Inhibitors and RNA interference were used to examine the signaling pathway regulated by the kinases. The obtained data demonstrated that CUR induces chemoresistant cell apoptosis by generating ROS and application of N-acetylcysteine (NAC) blocks ROS production, resulting in apoptosis suppression. Phosphorylation of extracellular regulated kinase (ERK), p38 MAPK, and eIF-2α were increased but c-Jun N-terminal kinase (JNK) did not increase when chemoresistant cells were treated with CUR. Downregulation of ERK and p38 MAPK phosphorylation by their inhibitors had no effect on CUR-induced apoptosis. Interestingly, the knockdown of p38 MAPK with shRNA significantly reduced CUR-induced apoptosis on the chemoresistant sublines. Phosphorylation of the eIF-2α protein was inhibited when p38 MAPK was knocked down in DOC-resistant A549 cells, but a high level of phosphorylated eIF-2α protein remained on the VCR-resistant A549 cells when p38 MAPK was knocked down. These data confirmed that CUR-augmented ROS potently induced apoptosis via upregulated p38 MAPK phosphorylation. Therefore, activated p38 MAPK is considered a pro-apoptotic signal for CUR-induced apoptosis of chemoresistant human lung cancer cells.
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21
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Rossi RE, Chen J, Caplin ME. The Role of Diet and Supplements in the Prevention and Progression of COVID-19: Current Knowledge and Open Issues. Prev Nutr Food Sci 2022; 27:137-149. [PMID: 35919576 PMCID: PMC9309075 DOI: 10.3746/pnf.2022.27.2.137] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Revised: 02/22/2022] [Accepted: 03/22/2022] [Indexed: 01/08/2023] Open
Abstract
A healthy diet and dietary supplements have gained attention as potential co-adjuvants in managing and preventing coronavirus disease 2019 (COVID-19). This paper critically reviews the current evidence regarding the impact of diet and supplements on the prevention and progression of COVID-19. According to available data, a healthy diet and normal weight are considered protective factors. Regarding dietary supplementation, the most robust results from human studies are for vitamin C, which appears to decrease inflammatory markers and suppress cytokine storm. A small, randomized trial showed that a high dose of vitamin D significantly reduced the need for intensive care unit treatment of patients requiring hospitalization for COVID-19. According to retrospective human studies, there is limited evidence for vitamin E and selenium supplements. Animal studies have investigated the effects of green tea and curcumin. Xanthohumol and probiotics, interesting for their antiviral, anti-inflammatory, and immunoregulatory properties, need formal clinical study. In summary, there is promising evidence supporting the role of diet and supplements as co-adjuvants in the treatment of COVID-19. Further studies and properly designed clinical trials are necessary to draw more robust conclusions; however, it is not unreasonable to take a pragmatic approach and promote the use of appropriate diet and supplements to counter the effects of COVID-19, ideally with a mechanism to assess outcomes.
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Affiliation(s)
- Roberta Elisa Rossi
- Hepatology and Hepato-Pancreatic-Biliary Surgery and Liver Transplantation, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, MI 20133, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, MI 20122, Italy
| | - Jie Chen
- Department of Gastroenterology, First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510275, China
| | - Martyn Evan Caplin
- Centre for Gastroenterology, Royal Free Hospital, London NW3 2QG, UK
- Division of Medicine, Faculty of Medical Sciences, University College London, London WC1E 6BT, UK
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22
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Wang X, Liu Z, Wang Y, Gou S. Platinum(IV) Prodrugs with Cancer Stem Cell Inhibitory Effects on Lung Cancer for Overcoming Drug Resistance. J Med Chem 2022; 65:7933-7945. [PMID: 35635560 DOI: 10.1021/acs.jmedchem.2c00472] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Affiliation(s)
- Xinyi Wang
- Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, PR China
- Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China
| | - Zhikun Liu
- Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, PR China
- Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China
| | - Yuanjiang Wang
- Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, PR China
- Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China
| | - Shaohua Gou
- Jiangsu Province Hi-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, PR China
- Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, PR China
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23
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Alesci A, Aragona M, Cicero N, Lauriano ER. Can nutraceuticals assist treatment and improve covid-19 symptoms? Nat Prod Res 2022; 36:2672-2691. [PMID: 33949266 DOI: 10.1080/14786419.2021.1914032] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
Viral diseases have always played an important role in public and individual health. Since December 2019, the world is facing a pandemic of SARS-CoV-2, a coronavirus that results in a syndrome known as COVID-19. Several studies were conducted to implement antiviral drug therapy, until the arrival of SARS-CoV-2 vaccines. Numerous scientific investigations have considered some nutraceuticals as an additional treatment of COVID-19 patients to improve their clinical picture. In this review, we would like to emphasize the studies conducted to date about this issue and try to understand whether the use of nutraceuticals as a supplementary therapy to COVID-19 may be a valid and viable avenue. Based on the results obtained so far, quercetin, astaxanthin, luteolin, glycyrrhizin, lactoferrin, hesperidin and curcumin have shown encouraging data suggesting their use to prevent and counteract the symptoms of this pandemic infection.
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Affiliation(s)
- Alessio Alesci
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
| | - Marialuisa Aragona
- Department of Veterinary Sciences, University of Messina, Messina, Italy
| | - Nicola Cicero
- Department of Biomedical and Dental Science and Morphofunctional Imaging, University of Messina, Messina, Italy
| | - Eugenia Rita Lauriano
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Messina, Italy
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24
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Memarzia A, Saadat S, Behrouz S, Boskabady MH. Curcuma longa and curcumin affect respiratory and allergic disorders, experimental and clinical evidence: A comprehensive and updated review. Biofactors 2022; 48:521-551. [PMID: 34932258 DOI: 10.1002/biof.1818] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Accepted: 12/05/2021] [Indexed: 01/23/2023]
Abstract
Curcuma longa and its constituents, mainly curcumin, showed various of pharmacological effects in previous studies. This review article provides updated and comprehensive experimental and clinical evidence regarding the effects of C. longa and curcumin on respiratory, allergic, and immunologic disorders. Using appropriate keywords, databases including PubMed, Science Direct, and Scopus were searched until the end of October 2021. C. longa extracts and its constituent, curcumin, showed the relaxant effect on tracheal smooth muscle, which indicates their bronchodilatory effect in obstructive pulmonary diseases. The preventive effects of extracts of C. longa and curcumin were shown in experimental animal models of different respiratory diseases through antioxidant, immunomodulatory, and anti-inflammatory mechanisms. C. longa and curcumin also showed preventive effects on some lung disorders in the clinical studies. It was shown that the effects of C. longa on pulmonary diseases were mainly due to its constituent, curcumin. Pharmacological effects of C. longa extracts and curcumin on respiratory, allergic, and immunologic disorders indicate the possible therapeutic effect of the plant and curcumin on these diseases.
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Affiliation(s)
- Arghavan Memarzia
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Saeideh Saadat
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, School of Medicine, Zahedan University of Medical Sciences, Zahedan, Iran
| | - Sepideh Behrouz
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohammad Hossein Boskabady
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Physiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
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25
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Ma C, Hu K, Ullah I, Zheng QK, Zhang N, Sun ZG. Molecular Mechanisms Involving the Sonic Hedgehog Pathway in Lung Cancer Therapy: Recent Advances. Front Oncol 2022; 12:729088. [PMID: 35433472 PMCID: PMC9010822 DOI: 10.3389/fonc.2022.729088] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2021] [Accepted: 03/03/2022] [Indexed: 12/09/2022] Open
Abstract
According to the latest statistics from the International Agency for Research on Cancer (IARC), lung cancer is one of the most lethal malignancies in the world, accounting for approximately 18% of all cancer-associated deaths. Yet, even with aggressive interventions for advanced lung cancer, the five-year survival rate remains low, at around 15%. The hedgehog signaling pathway is highly conserved during embryonic development and is involved in tissue homeostasis as well as organ development. However, studies have documented an increasing prevalence of aberrant activation of HH signaling in lung cancer patients, promoting malignant lung cancer progression with poor prognostic outcomes. Inhibitors targeting the HH pathway have been widely used in tumor therapy, however, they still cannot avoid the occurrence of drug resistance. Interestingly, natural products, either alone or in combination with chemotherapy, have greatly improved overall survival outcomes for lung cancer patients by acting on the HH signaling pathway because of its unique and excellent pharmacological properties. In this review, we elucidate on the underlying molecular mechanisms through which the HH pathway promotes malignant biological behaviors in lung cancer, as well as the potential of inhibitors or natural compounds in targeting HH signaling for clinical applications in lung cancer therapy.
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Affiliation(s)
- Chao Ma
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Kang Hu
- School of Clinical Medicine, Weifang Medical University, Weifang, China
- Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Irfan Ullah
- Department of Surgery, Khyber Medical University Peshawar, Peshawar, Pakistan
| | - Qing-Kang Zheng
- School of Clinical Medicine, Weifang Medical University, Weifang, China
| | - Nan Zhang
- Breast Center, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
| | - Zhi-Gang Sun
- Department of Thoracic Surgery, Central Hospital Affiliated to Shandong First Medical University, Jinan, China
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26
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Bisdemethoxycurcumin sensitizes the response of cisplatin resistant non-small cell lung carcinoma cell lines by activating apoptosis and autophagy. J Nutr Biochem 2022; 106:109003. [PMID: 35346827 DOI: 10.1016/j.jnutbio.2022.109003] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2021] [Revised: 11/24/2021] [Accepted: 02/25/2022] [Indexed: 01/11/2023]
Abstract
Lung cancer belongs to the most frequent and deadliest cancer types worldwide, non-small cell lung carcinoma (NSCLC) being the most frequent type. Development of chemoresistance in NSCLC patients is common and responsible for bad outcome. Curcuminoids are naturally occurring substances with prominent cytotoxic effects in different cancer cells. Here we analyzed influence of bisdemethoxycurcumin (BDMC) on phenotype and molecular mechanisms in cisplatin-sensitive NSCLC cell lines (A549 and H460) and their cisplatin-resistant counterparts. NSCLC cell lines were exposed to BDMC and analyzed by cell viability, proliferation, and motility assays, as well as fluorescence-activated cell sorting. Immunoblotting was assessed to detect apoptosis and autophagy. Colony-formation assay and multicellular tumor spheroid model were used to investigate the effects of BDMC. Expression levels of different Hedgehog-pathway genes were determined by RT-qPCR analysis. We identified substantial cytotoxic effects of BDMC on NSCLC cells in general and on cisplatin-resistant NSCLC cells in special. BDMC markedly decreased the cell viability by inducing apoptosis and autophagy in a cell-type specific manner. BDMC emphasized cisplatin-induced cell death and inhibited cell cycle progression of cisplatin-resistant NSCLC cells. Scratch-closure, colony formation, and multicellular spheroid growth in cisplatin-resistant NSCLC cell lines were inhibited by BDMC. Expression profile analyses of different Hedgehog-pathway regulatory genes showed that Gli1, the mean transcriptional regulator of this pathway, was markedly decreased upon the BDMC treatment, this decrement being most prominent in cisplatin-resistant cells. Our data identified BDMC as a potent substance that may be suitable for combined cisplatin-based therapy in cisplatin-resistant subpopulation of NSCLC patients.
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27
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Jie Z, Jinna Z, Jingjun Z, Pengcheng L, Fang Y, Qinyang C, Taiyu C, Hequn J, Tao R. Antitumor Effects of 10058-F4 and Curcumin in Combination Therapy for Pancreatic Cancer In Vitro and In Vivo. JOURNAL OF HEALTHCARE ENGINEERING 2022; 2022:1620802. [PMID: 35368919 PMCID: PMC8970865 DOI: 10.1155/2022/1620802] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/10/2022] [Revised: 02/28/2022] [Accepted: 03/02/2022] [Indexed: 12/30/2022]
Abstract
BACKGROUND Pancreatic cancer (PC) stands out as one of the most lethal cancers. Due to late diagnosis, only a fraction of patients can be resected. Although it still has significant adverse effects and poor results, the treatment is connected with better overall survival than the prior treatment. Thus, new alternative therapy for advanced PC is needed. Materials/Methods. The impact of 10058-F4 and curcumin combination therapy on apoptosis and cell growth in SW1990 pancreatic cancer cells were determined in vitro using the CCK-8 assay and flow cytometry of Annexin V-FITC/PI, and the in vivo antitumor effect was determined utilizing SW1990-bearing pancreatic tumor mouse models induced by subcutaneous implantation. RESULTS At concentrations of (10 mol/L+2 mol/L), 10058-F4+curcumin obtained the highest rate of SW1990 cell death, and they had a beneficial effect on SW1990 pancreatic tumor-bearing animals. Furthermore, c-Myc, Akt phosphorylation, and the expression of apoptosis-related molecular were reduced, and the combination therapy modified the expression of apoptosis-related molecular. CONCLUSIONS In vitro and in vivo, the combination of 10058-F4 plus curcumin has antipancreatic cancer actions that are substantially effective.
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Affiliation(s)
- Zhang Jie
- Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Si Chuan, China
| | - Zhang Jinna
- No.4 West China Teaching Hospital of Si Chuan University, Si Chuan, China
| | - Zhang Jingjun
- The People's Hospital of JianYang City, Si Chuan, China
| | - Li Pengcheng
- Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Si Chuan, China
| | - Yang Fang
- Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Si Chuan, China
| | | | - Chen Taiyu
- Chengdu Medical College, Si Chuan, China
| | - Jiang Hequn
- South China Hospital of Shenzhen University, Guang Dong, China
| | - Ren Tao
- Clinical Medical College and The First Affiliated Hospital of Chengdu Medical College, Si Chuan, China
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28
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Pan Z, Liu H, Chen J. [Lung Cancer Stem-like Cells and Drug Resistance]. ZHONGGUO FEI AI ZA ZHI = CHINESE JOURNAL OF LUNG CANCER 2022; 25:111-117. [PMID: 35224964 PMCID: PMC8913289 DOI: 10.3779/j.issn.1009-3419.2022.102.02] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Lung cancer remains the leading cause of cancer-related death world-wide. Therapy resistance and relapse are considered major reasons contributing to the poor survival rates of lung cancer. Accumulated evidences have demonstrated that a small subpopulation of stem-like cells existed within lung cancer tissues and cell lines, possessing the abilities of self-renewal, multipotent differentiation and unlimited proliferation. These lung cancer stem-like cells (LCSCs) can generate tumors with high effeciency in vivo, survive cytotoxic therapies, and eventually lead to therapy resistance and recurrence. In this review, we would like to present recent knowledges on LCSCs, including the origins where they come from, the molecular features to identify them, and key mechanisms for them to survive and develop resistance, in order to provide a better view for targeting them in future clinic.
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Affiliation(s)
- Zhenhua Pan
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin 300052, China
| | - Hongyu Liu
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin 300052, China
| | - Jun Chen
- Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin 300052, China.,Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China
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29
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Asadirad A, Nashibi R, Khodadadi A, Ghadiri AA, Sadeghi M, Aminian A, Dehnavi S. Antiinflammatory potential of nano-curcumin as an alternative therapeutic agent for the treatment of mild-to-moderate hospitalized COVID-19 patients in a placebo-controlled clinical trial. Phytother Res 2022; 36:1023-1031. [PMID: 35040210 DOI: 10.1002/ptr.7375] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2021] [Revised: 12/11/2021] [Accepted: 12/22/2021] [Indexed: 12/18/2022]
Abstract
The present study conducted a placebo-controlled clinical trial to evaluate the impact of nano-curcumin on the inflammatory cytokines in mild-to-moderate hospitalized COVID-19 patients. A total of 60 COVID-19 patients were randomly divided into nano-curcumin and control groups, and then they received 240 mg/day nano-curcumin for 7 days. The clinical manifestation and laboratory parameters in patients were recorded on days 0 and seven. Also, SYBR Green real-time PCR and ELISA techniques were implicated in assessing the mRNA expression of IFN-γ, IL-1β, IL-6, MCP-1, and TNF-α and the serum levels of IL-1β, IL-6, and TNF-α inflammatory mediators, respectively. Although the clinical manifestations and laboratory parameters improved via the nano-curcumin treatment, the mRNA expression of IFN-γ (p = 0.006) and TNF-α (p = 0.04) were significantly reduced. Besides, a considerable difference was observed between the nano-curcumin and control groups in the expression of IFN-γ (p = 0.001), IL-1β (p = 0.0002), and IL-6 (p = 0.008). In addition, there was a significant difference between the nano-curcumin and control groups in the serum levels of IL-1β (p = 0.042). The evidence demonstrated that nano-curcumin could be implicated as a complementary medication to act as an antiinflammatory agent and inhibit inflammatory complications.
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Affiliation(s)
- Ali Asadirad
- Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Roohangiz Nashibi
- Infectious and Tropical Diseases Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ali Khodadadi
- Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Ata A Ghadiri
- Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Mahvash Sadeghi
- Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Azam Aminian
- Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
- Department of Nursing, School of Nursing and Midwifery, Ilam University of Medical Sciences, Ilam, Iran
| | - Sajad Dehnavi
- Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
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30
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Ullah MF, Ahmad A, Bhat SH, Abuduhier FM, Mustafa SK, Usmani S. Diet-derived small molecules (nutraceuticals) inhibit cellular proliferation by interfering with key oncogenic pathways: an overview of experimental evidence in cancer chemoprevention. Biol Futur 2022; 73:55-69. [PMID: 35040098 DOI: 10.1007/s42977-022-00110-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2021] [Accepted: 01/07/2022] [Indexed: 10/19/2022]
Abstract
Discouraging statistics of cancer disease has projected an increase in the global cancer burden from 19.3 to 28.4 million incidences annually within the next two decades. Currently, there has been a revival of interest in nutraceuticals with evidence of pharmacological properties against human diseases including cancer. Diet is an integral part of lifestyle, and it has been proposed that an estimated one-third of human cancers can be prevented through appropriate lifestyle modification including dietary habits; hence, it is considered significant to explore the pharmacological benefits of these agents, which are easily accessible and have higher safety index. Accordingly, an impressive embodiment of evidence supports the concept that the dietary factors are critical modulators to prevent, retard, block, or reverse carcinogenesis. Such an action reflects the ability of these molecules to interfere with multitude of pathways to subdue and neutralize several oncogenic factors and thereby keep a restraint on neoplastic transformations. This review provides a series of experimental evidence based on the current literature to highlight the translational potential of nutraceuticals for the prevention of the disease through consumption of enriched diets and its efficacious management by means of novel interventions. Specifically, this review provides the current understanding of the chemopreventive pharmacology of nutraceuticals such as cucurbitacins, morin, fisetin, curcumin, luteolin and garcinol toward their potential as anticancer agents.
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Affiliation(s)
- Mohammad Fahad Ullah
- Prince Fahd Research Chair, Department of Medical Laboratory Technology, Faculty of Applied Medical Science, University of Tabuk, Tabuk, Saudi Arabia.
| | - Aamir Ahmad
- University of Alabama at Birmingham, Birmingham, AL, USA
- Interim Translational Research Institute, Hamad Medical Corporation, Doha, Qatar
| | - Showket H Bhat
- Prince Fahd Research Chair, Department of Medical Laboratory Technology, Faculty of Applied Medical Science, University of Tabuk, Tabuk, Saudi Arabia
- Department of Medical Laboratory Technology and Molecular Diagnostics, Center for Vocational Studies, Islamic University of Science and Technology, Awantipora, Jammu & Kashmir, India
| | - Faisel M Abuduhier
- Prince Fahd Research Chair, Department of Medical Laboratory Technology, Faculty of Applied Medical Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Syed Khalid Mustafa
- Department of Chemistry, Faculty of Science, University of Tabuk, Tabuk, Saudi Arabia
| | - Shazia Usmani
- Faculty of Pharmacy, Integral University, Lucknow, India
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31
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Hu A, Hu Z, Ye J, Liu Y, Lai Z, Zhang M, Ji W, Huang L, Zou H, Chen B, Zhong J. Metformin exerts anti-tumor effects via Sonic hedgehog signaling pathway by targeting AMPK in HepG2 cells. Biochem Cell Biol 2022; 100:142-151. [PMID: 34990285 DOI: 10.1139/bcb-2021-0409] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022] Open
Abstract
Metformin, a traditional first-line pharmacologic treatment for type 2 diabetes, has recently been shown to impart anti-cancer effects on hepatocellular carcinoma (HCC). However, the molecular mechanism of metformin on its antitumor activity is still not completely clear. The Sonic hedgehog (Shh) signaling pathway is closely associated with the initiation and progression of HCC. Therefore, the aim of the current study was to investigate the effects of metformin on the biological behavior of HCC and the underlying functional mechanism of metformin on the Shh pathway. The HCC cellular was induced in HepG2 cells by recombinant human Shh (rhShh). The effects of metformin on proliferation and metastasis were evaluated by proliferation, wound healing and invasion assays in vitro. The mRNA and protein expression levels of proteins related to the Shh pathway were measured by western blotting, quantitative PCR and immunofluorescence staining. Metformin inhibited rhShh-induced proliferation and metastasis. Furthermore, metformin decreased mRNA and protein expression of components of the Shh pathway including Shh, Ptch, Smo and Gli-1. Silencing of AMPK in the presence of metformin revealed that metformin could exert its inhibitory effect via AMPK. Our findings demonstrate that metformin can suppress the migration and invasion of HepG2 cells via AMPK-mediated inhibition of the Shh pathway.
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Affiliation(s)
- Ang Hu
- Gannan Medical University, 74554, Ganzhou, Jiangxi, China;
| | - Zeming Hu
- First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China;
| | - Jianming Ye
- First Affiliated Hospital of Gannan Medical University, 477808, Ganzhou, Jiangxi, China;
| | - Yuwen Liu
- Gannan Medical University, 74554, Ganzhou, Jiangxi, China;
| | - Zhonghong Lai
- Gannan Medical University, 74554, Ganzhou, Jiangxi, China;
| | - Mi Zhang
- Gannan Medical University, 74554, Ganzhou, Jiangxi, China;
| | - Weichao Ji
- Gannan Medical University, 74554, Ganzhou, Jiangxi, China;
| | - Lili Huang
- Gannan Medical University, 74554, Ganzhou, Jiangxi, China;
| | - Haohong Zou
- Gannan Medical University, 74554, Ganzhou, Jiangxi, China;
| | - Bin Chen
- First Affiliated Hospital of Gannan Medical University, 477808, Ganzhou, Jiangxi, China;
| | - Jianing Zhong
- Gannan Medical University, 74554, Ganzhou, China, 341000;
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32
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Cortes-Dericks L, Galetta D. Impact of Cancer Stem Cells and Cancer Stem Cell-Driven Drug Resiliency in Lung Tumor: Options in Sight. Cancers (Basel) 2022; 14:267. [PMID: 35053430 PMCID: PMC8773978 DOI: 10.3390/cancers14020267] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/30/2021] [Revised: 12/20/2021] [Accepted: 01/04/2022] [Indexed: 12/12/2022] Open
Abstract
Causing a high mortality rate worldwide, lung cancer remains an incurable malignancy resistant to conventional therapy. Despite the discovery of specific molecular targets and new treatment strategies, there remains a pressing need to develop more efficient therapy to further improve the management of this disease. Cancer stem cells (CSCs) are considered the root of sustained tumor growth. This consensus corroborates the CSC model asserting that a distinct subpopulation of malignant cells within a tumor drives and maintains tumor progression with high heterogeneity. Besides being highly tumorigenic, CSCs are highly refractory to standard drugs; therefore, cancer treatment should be focused on eliminating these cells. Herein, we present the current knowledge of the existence of CSCs, CSC-associated mechanisms of chemoresistance, the ability of CSCs to evade immune surveillance, and potential CSC inhibitors in lung cancer, to provide a wider insight to drive a more efficient elimination of this pro-oncogenic and treatment-resistant cell fraction.
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Affiliation(s)
| | - Domenico Galetta
- Division of Thoracic Surgery, European Institute of Oncology, IRCCS, 20141 Milan, Italy;
- Department of Oncology and Hematology-Oncology-DIPO, University of Milan, 20122 Milan, Italy
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33
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Hao M, Chu Y, Lei J, Yao Z, Wang P, Chen Z, Wang K, Sang X, Han X, Wang L, Cao G. Pharmacological Mechanisms and Clinical Applications of Curcumin: Update. Aging Dis 2022; 14:716-749. [PMID: 37191432 DOI: 10.14336/ad.2022.1101] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2022] [Accepted: 11/01/2022] [Indexed: 11/19/2022] Open
Abstract
Curcumin, a well-known hydrophobic polyphenol extracted from the rhizomes of turmeric (Curcuma longa L.), has attracted great interest in the last ten years due to its multiple pharmacological activities. A growing body of evidence has manifested that curcumin has extensive pharmacological activities including anti-inflammatory, anti-oxygenation, lipid regulation, antiviral, and anticancer with hypotoxicity and minor adverse reactions. However, the disadvantages of low bioavailability, short half-life in plasma, low drug concentration in blood, and poor oral absorption severely limited the clinical application of curcumin. Pharmaceutical researchers have carried out plenty of dosage form transformations to improve the druggability of curcumin and have achieved remarkable results. Therefore, the objective of this review summarizes the pharmacological research progress, problems in clinical application and the improvement methods of curcumin's druggability. By reviewing the latest research progress of curcumin, we believe that curcumin has a broad clinical application prospect for its wide range of pharmacological activities with few side effects. The deficiencies of lower bioavailability of curcumin could be improved by dosage form transformation. However, curcumin in the clinical application still requires further study regarding the underlying mechanism and clinical trial verification.
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34
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Benameur T, Giacomucci G, Panaro MA, Ruggiero M, Trotta T, Monda V, Pizzolorusso I, Lofrumento DD, Porro C, Messina G. New Promising Therapeutic Avenues of Curcumin in Brain Diseases. Molecules 2021; 27:236. [PMID: 35011468 PMCID: PMC8746812 DOI: 10.3390/molecules27010236] [Citation(s) in RCA: 51] [Impact Index Per Article: 12.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 12/28/2021] [Accepted: 12/29/2021] [Indexed: 01/02/2023] Open
Abstract
Curcumin, the dietary polyphenol isolated from Curcuma longa (turmeric), is commonly used as an herb and spice worldwide. Because of its bio-pharmacological effects curcumin is also called "spice of life", in fact it is recognized that curcumin possesses important proprieties such as anti-oxidant, anti-inflammatory, anti-microbial, antiproliferative, anti-tumoral, and anti-aging. Neurodegenerative diseases such as Alzheimer's Diseases, Parkinson's Diseases, and Multiple Sclerosis are a group of diseases characterized by a progressive loss of brain structure and function due to neuronal death; at present there is no effective treatment to cure these diseases. The protective effect of curcumin against some neurodegenerative diseases has been proven by in vivo and in vitro studies. The current review highlights the latest findings on the neuroprotective effects of curcumin, its bioavailability, its mechanism of action and its possible application for the prevention or treatment of neurodegenerative disorders.
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Affiliation(s)
- Tarek Benameur
- Department of Biomedical Sciences, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia;
| | - Giulia Giacomucci
- Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, 50134 Florence, Italy;
| | - Maria Antonietta Panaro
- Biotechnologies and Biopharmaceutics, Department of Biosciences, University of Bari, 70125 Bari, Italy; (M.A.P.); (M.R.)
| | - Melania Ruggiero
- Biotechnologies and Biopharmaceutics, Department of Biosciences, University of Bari, 70125 Bari, Italy; (M.A.P.); (M.R.)
| | - Teresa Trotta
- Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy; (T.T.); (V.M.); (G.M.)
| | - Vincenzo Monda
- Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy; (T.T.); (V.M.); (G.M.)
- Unit of Dietetic and Sport Medicine, Section of Human Physiology, Department of Experimental Medicine, Luigi Vanvitelli University of Campania, 81100 Naples, Italy
| | - Ilaria Pizzolorusso
- Child and Adolescent Neuropsychiatry Unit, Department of Mental Health, ASL Foggia, 71121 Foggia, Italy;
| | - Dario Domenico Lofrumento
- Department of Biological and Environmental Sciences and Technologies, Section of Human Anatomy, University of Salento, 73100 Lecce, Italy;
| | - Chiara Porro
- Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy; (T.T.); (V.M.); (G.M.)
| | - Giovanni Messina
- Department of Clinical and Experimental Medicine, University of Foggia, 71121 Foggia, Italy; (T.T.); (V.M.); (G.M.)
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Targeting Cancer Stem Cells by Dietary Agents: An Important Therapeutic Strategy against Human Malignancies. Int J Mol Sci 2021; 22:ijms222111669. [PMID: 34769099 PMCID: PMC8584029 DOI: 10.3390/ijms222111669] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2021] [Revised: 10/23/2021] [Accepted: 10/23/2021] [Indexed: 02/07/2023] Open
Abstract
As a multifactorial disease, treatment of cancer depends on understanding unique mechanisms involved in its progression. The cancer stem cells (CSCs) are responsible for tumor stemness and by enhancing colony formation, proliferation as well as metastasis, and these cells can also mediate resistance to therapy. Furthermore, the presence of CSCs leads to cancer recurrence and therefore their complete eradication can have immense therapeutic benefits. The present review focuses on targeting CSCs by natural products in cancer therapy. The growth and colony formation capacities of CSCs have been reported can be attenuated by the dietary agents. These compounds can induce apoptosis in CSCs and reduce tumor migration and invasion via EMT inhibition. A variety of molecular pathways including STAT3, Wnt/β-catenin, Sonic Hedgehog, Gli1 and NF-κB undergo down-regulation by dietary agents in suppressing CSC features. Upon exposure to natural agents, a significant decrease occurs in levels of CSC markers including CD44, CD133, ALDH1, Oct4 and Nanog to impair cancer stemness. Furthermore, CSC suppression by dietary agents can enhance sensitivity of tumors to chemotherapy and radiotherapy. In addition to in vitro studies, as well as experiments on the different preclinical models have shown capacity of natural products in suppressing cancer stemness. Furthermore, use of nanostructures for improving therapeutic impact of dietary agents is recommended to rapidly translate preclinical findings for clinical use.
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Chang M, Shang M, Yuan F, Guo W, Wang C. EF24 exerts cytotoxicity against NSCLC via inducing ROS accumulation. Cancer Cell Int 2021; 21:531. [PMID: 34641863 PMCID: PMC8513219 DOI: 10.1186/s12935-021-02240-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/23/2021] [Accepted: 09/29/2021] [Indexed: 12/11/2022] Open
Abstract
Background The role of Diphenyldifluoroketone (EF24), a synthetic analogue of curcumin with noteworthy antitumor potential, remains unclear in non-small cell lung cancer (NSCLC). Herein, the inhibitory effect of EF24 on NSCLC and its mechanism were studied. Methods Cytotoxicity was measured by MTT assay, colony formation assay and xenograft model. Cell apoptosis and reactive oxygen species (ROS) level were quantified by flow cytometer. Protein level was detected by western blot assay. Mitochondria and autophagosomes were observed using transmission electron microscope and confocal microscopy. Results In-vitro, EF24 significantly induced proliferation inhibition, apoptosis, mitochondrial fission and autophagy of NSCLC cell lines. These cytotoxic effects were significantly attenuated by two reactive oxygen species (ROS) scavengers, indicating its anti-cancer effects largely depend on ROS accumulation. In-vivo, EF24 inhibited tumor growth in a dose-dependent manner. Moreover, no pathological changes of heart, lung, spleen, kidney and liver of mice were observed. Collectively, EF24 induced ROS accumulation, in turn activates cell apoptosis, and then exerts its cytotoxicity on NSCLC cells. Conclusions The results showed that EF24 exerted cytotoxicity against NSCLC via ROS accumulation. Thus, EF24 might serve as a potential anti-cancer agent for the treatment of NSCLC. Supplementary Information The online version contains supplementary material available at 10.1186/s12935-021-02240-z.
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Affiliation(s)
- Minghui Chang
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China
| | - Ming Shang
- Department of Clinical Laboratory, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China
| | - Fang Yuan
- Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People's Republic of China
| | - Wei Guo
- Ultrasound Diagnosis Department, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, Shandong, People's Republic of China.
| | - Cuijuan Wang
- Physical and Chemical Laboratory, Shandong Academy of Occupational Health and Occupational Medicine, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, 250000, People's Republic of China.
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Malla RR, Padmaraju V, Marni R, Kamal MA. Natural products: Potential targets of TME related long non-coding RNAs in lung cancer. PHYTOMEDICINE 2021; 93:153782. [PMID: 34627097 DOI: 10.1016/j.phymed.2021.153782] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 09/08/2021] [Accepted: 09/26/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Lung cancer is a significant health concern worldwide due to high mortality and morbidity, despite the advances in diagnosis, treatment, and management. Recent experimental evidence from different models suggested long non-coding RNAs (lncRNAs) as major modulators of cancer stem cells (CSCs) in the tumor microenvironment (TME) to support metastasis and drug resistance in lung cancer. Evidence-based studies demonstrated that natural products interfere with TME functions. PURPOSE OF STUDY To establish lncRNAs of TME as novel targets of natural compounds for lung cancer management. STUDY DESIGN Current study used a combination of TME and lung CSCs, lncRNAs and enrichment and stemness maintenance, natural products and stem cell management, natural products and lncRNAs, natural products and targeted delivery as keywords to retrieve the literature from Scopus, Web of Science, PubMed, and Google Scholar. This study critically reviewed the current literature and presented cancer stem cells' ability in reprogramming lung TME. RESULTS This review found that TME related oncogenic and tumor suppressor lncRNAs and their signaling pathways control the maintenance of stemness in lung TME. This review explored natural phenolic compounds and found that curcumin, genistein, quercetin epigallocatechin gallate and ginsenoside Rh2 are efficient in managing lung CSCs. They modulate lncRNAs and their upstream mediators by targeting signaling and epigenetic pathways. This review also identified relevant nanotechnology-based phytochemical delivery approaches for targeting lung cancer. CONCLUSION By critical literature analysis, TME related lncRNAs were identified as potential therapeutic targets, aiming to develop natural product-based therapeutics to treat metastatic and drug-resistant lung cancers.
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Affiliation(s)
- Rama Rao Malla
- Cancer Biology Lab, Department of Biochemistry and Bioinformatics, GIS, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh 530045, India; Department of Biochemistry and Bioinformatics, GIS, GITAM (Deemed to be) University, Visakhapatnam, Andhra Pradesh 530045, India.
| | - Vasudevaraju Padmaraju
- Department of Biochemistry and Bioinformatics, GIS, GITAM (Deemed to be) University, Visakhapatnam, Andhra Pradesh 530045, India
| | - Rakshmitha Marni
- Cancer Biology Lab, Department of Biochemistry and Bioinformatics, GIS, GITAM (Deemed to be University), Visakhapatnam, Andhra Pradesh 530045, India; Department of Biochemistry and Bioinformatics, GIS, GITAM (Deemed to be) University, Visakhapatnam, Andhra Pradesh 530045, India
| | - Mohammad Amjad Kamal
- West China School of Nursing / Institutes for Systems Genetics, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, China; King Fahd Medical Research Center, King Abdulaziz University, P. O. Box 80216, Jeddah 21589, Saudi Arabia; Enzymoics, Novel Global Community Educational Foundation, Australia
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Maleki Dana P, Sadoughi F, Mansournia MA, Mirzaei H, Asemi Z, Yousefi B. Targeting Wnt signaling pathway by polyphenols: implication for aging and age-related diseases. Biogerontology 2021; 22:479-494. [PMID: 34480268 DOI: 10.1007/s10522-021-09934-x] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2021] [Accepted: 08/26/2021] [Indexed: 12/14/2022]
Abstract
Age is an important risk factor for different diseases. The same mechanisms that promote aging are involved in the development and progression of age-associated diseases. Polyphenols are organic compounds found in fruits and vegetables. Due to their beneficial properties (e.g. antioxidant and anti-inflammatory), polyphenols have been extensively used for treating chronic diseases. To exert their functions, polyphenols target various molecular mechanisms and signaling pathways, such as mTOR, NF-κB, and Wnt/β-catenin. Wnt signaling is a critical pathway for developmental processes. Besides, dysregulation of this signaling pathway has been observed in various diseases. Several investigations have been conducted on Wnt inhibitors at pre-clinical stages, showing promising results. Herein, we review the studies dealing with the role of polyphenols in targeting the Wnt signaling pathways in aging processes and age-associated diseases, including cancer, diabetes, Alzheimer's disease, osteoporosis, and Parkinson's disease.
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Affiliation(s)
- Parisa Maleki Dana
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Fatemeh Sadoughi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Mohammad Ali Mansournia
- Department of Epidemiology and Biostatistics, School of Public Health, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Hamed Mirzaei
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, Islamic Republic of Iran.
| | - Bahman Yousefi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.
- Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Islamic Republic of Iran.
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Pashirzad M, Johnston TP, Sahebkar A. Therapeutic Effects of Polyphenols on the Treatment of Colorectal Cancer by Regulating Wnt β-Catenin Signaling Pathway. JOURNAL OF ONCOLOGY 2021; 2021:3619510. [PMID: 34621313 PMCID: PMC8492275 DOI: 10.1155/2021/3619510] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/17/2021] [Accepted: 09/17/2021] [Indexed: 12/16/2022]
Abstract
Colorectal cancer (CRC) is the third most common cause of cancer-related death worldwide in terms of both its rates of incidence and mortality. Due to serious side effects associated with conventional chemotherapeutic treatments, many natural products with fewer adverse side effects have been considered as potential treatment options. In fact, many natural products have widely been used in various phases of clinical trials for CRC, as well as in in vitro and in vivo preclinical studies. Curcumin (CUR) and resveratrol (RES) are classified as natural polyphenolic compounds that have been demonstrated to have anticancer activity against CRC and are associated with minimal side effects. By regulating select target genes involved in several key signaling pathways in CRC, in particular, the Wnt β-catenin signaling cascade, the course of CRC may be positively altered. In the current review, we focused on the therapeutic effects of CUR and RES in CRC as they pertain to modulation of the Wnt β-catenin signaling pathway.
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Affiliation(s)
- Mehran Pashirzad
- Department of Medical Biochemistry, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Thomas P. Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
- Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
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Phytochemical profile, in vitro antioxidant, and anti-protein denaturation activities of Curcuma longa L. rhizome and leaves. OPEN CHEM 2021. [DOI: 10.1515/chem-2021-0086] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
Abstract
Curcuma longa L. is a famous spice cultivated in many countries with significant variations reported in its phytochemical contents and biological potential. For the first time, the present work is aimed to identify the major phytochemicals present in methanol:chloroform (MC) and petroleum ether (PE) extracts of Curcuma longa rhizome and leaves (by determining polyphenols and GC/MS analysis), and their in-vitro antioxidant and anti-protein denaturation potential. Results showed that the highest value (P < 0.05) of polyphenolic content was in MC extract of rhizome (51.46 ± 0.46 mg GAE/g) followed by 31.20 ± 0.53 mg GAE/g in MC leaves extract. The strong antiradical activity was evaluated in MC extract of rhizome with IC50 value of 92 ± 0.02 µg/mL. MC extracts of both the rhizome and leaves exerted a potent inhibitory effect against protein denaturation with IC50 values of 106.21 ± 0.53 and 108.06 ± 4.67 μg/mL (P > 0.5), respectively. GC/MS analysis showed that α-tumerone was the main component in the rhizome oil (32.44%), whereas in the leaf oil, palmitic acid was the prominent constituent (28.33%) and α-phellandrene recorded a comparable percentage (7.29). In conclusion, C. longa is a valuable source of natural antioxidants and anti-inflammatory constituents, as indicated by its high polyphenolic content and by its considerable in vitro antiradical and anti-protein denaturation potential.
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Xie C, Zhou X, Liang C, Li X, Ge M, Chen Y, Yin J, Zhu J, Zhong C. Apatinib triggers autophagic and apoptotic cell death via VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling in lung cancer. JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH : CR 2021; 40:266. [PMID: 34429133 PMCID: PMC8385858 DOI: 10.1186/s13046-021-02069-4] [Citation(s) in RCA: 113] [Impact Index Per Article: 28.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Accepted: 08/10/2021] [Indexed: 11/26/2022]
Abstract
Background Recently, a variety of clinical trials have shown that apatinib, a small-molecule anti-angiogenic drug, exerts promising inhibitory effects on multiple solid tumors, including non-small cell lung cancer (NSCLC). However, the underlying molecular mechanism of apatinib on NSCLC remains unclear. Methods MTT, EdU, AO/EB staining, TUNEL staining, flow cytometry, colony formation assays were performed to investigate the effects of apatinib on cell proliferation, cell cycle distribution, apoptosis and cancer stem like properties. Wound healing and transwell assays were conducted to explore the role of apatinib on migration and invasion. The regulation of apatinib on VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling were detected. Furthermore, we collected conditioned medium (CM) from A549 and H1299 cells to stimulate phorbol myristate acetate (PMA)-activated THP-1 cells, and examined the effect of apatinib on PD-L1 expression in macrophages. The Jurkat T cells and NSCLC cells co-culture model was used to assess the effect of apatinib on T cells activation. Subcutaneous tumor formation models were established to evaluate the effects of apatinib in vivo. Histochemical, immunohistochemical staining and ELISA assay were used to examine the levels of signaling molecules in tumors. Results We showed that apatinib inhibited cell proliferation and promoted apoptosis in NSCLC cells in vitro. Apatinib induced cell cycle arrest at G1 phase and suppressed the expression of Cyclin D1 and CDK4. Moreover, apatinib upregulated Cleaved Caspase 3, Cleaved Caspase 9 and Bax, and downregulated Bcl-2 in NSCLC cells. The colony formation ability and the number of CD133 positive cells were significantly decreased by apatinib, suggesting that apatinib inhibited the malignant and stem-like features of NSCLC cells. Mechanistically, apatinib inhibited PD-L1 and c-Myc expression by targeting VEGFR2/STAT3 signaling. Apatinib also inhibited PD-L1 expression in THP-1 derived macrophages stimulated by CM from NSCLC cells. Furthermore, apatinib pretreatment increased CD69 expression and IFN-γ secretion in stimulated Jurkat T cells co-cultured with NSCLC cells. Apatinib also promoted ROS production and inhibited Nrf2 and p62 expression, leading to the autophagic and apoptotic cell death in NSCLC. Moreover, apatinib significantly inhibited tumor growth in vivo. Conclusion Our data indicated that apatinib induced autophagy and apoptosis in NSCLC via regulating VEGFR2/STAT3/PD-L1 and ROS/Nrf2/p62 signaling. Supplementary Information The online version contains supplementary material available at 10.1186/s13046-021-02069-4.
Apatinib suppressed proliferation, induced cell cycle arrest and apoptosis, and inhibited malignancy in NSCLC in vitro and in vivo. Apatinib downregulated PD-L1 and c-Myc in NSCLC through VEGFR2/STAT3 pathway. Apatinib inhibited PD-L1 expression in THP-1 derived macrophages stimulated by the conditioned medium from NSCLC cells and partially restored the activation of Jurkat T cells co-cultured with NSCLC cells. Apatinib induced ROS generation and inhibited Nrf2 and p62 expression, leading to the autophagic and apoptotic cell death in NSCLC.
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Affiliation(s)
- Chunfeng Xie
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing, 211166, China
| | - Xu Zhou
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing, 211166, China
| | - Chunhua Liang
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing, 211166, China
| | - Xiaoting Li
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing, 211166, China
| | - Miaomiao Ge
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing, 211166, China
| | - Yue Chen
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing, 211166, China
| | - Juan Yin
- Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Rd, Suzhou, 215008, China
| | - Jianyun Zhu
- Department of Laboratory, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, 242 Guangji Rd, Suzhou, 215008, China.
| | - Caiyun Zhong
- Department of Nutrition and Food Safety, School of Public Health, Nanjing Medical University, 101 Longmian Ave, Jiangning, Nanjing, 211166, China. .,Cancer Research Division, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, 211166, Jiangsu, China.
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Sulforaphane inhibits self-renewal of lung cancer stem cells through the modulation of sonic Hedgehog signaling pathway and polyhomeotic homolog 3. AMB Express 2021; 11:121. [PMID: 34424425 PMCID: PMC8382806 DOI: 10.1186/s13568-021-01281-x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 08/13/2021] [Indexed: 12/24/2022] Open
Abstract
Sulforaphane (SFN), an active compound in cruciferous vegetables, has been characterized by its antiproliferative capacity. We investigated the role and molecular mechanism through which SFN regulates proliferation and self-renewal of lung cancer stem cells. CD133+ cells were isolated with MACs from lung cancer A549 and H460 cells. In this study, we found that SFN inhibited the proliferation of lung cancer cells and self-renewal of lung cancer stem cells simultaneously. Meanwhile, the mRNA and protein expressions of Shh, Smo, Gli1 and PHC3 were highly activated in CD133+ lung cancer cells. Compared with siRNA-control group, Knock-down of Shh inhibited proliferation of CD133+ lung cancer cells, and decreased the protein expression of PHC3 in CD133+ lung cancer cells. Knock-down of PHC3 also affected the proliferation and decreased the Shh expression level in CD133+ lung cancer cells. In addition, SFN inhibited the activities of Shh, Smo, Gli1 and PHC3 in CD133+ lung cancer cells. Furthermore, the inhibitory effect of SFN on the proliferation of siRNA-Shh and siRNA-PHC3 cells was weaker than that on the proliferation of siRNA-control cells. Sonic Hedgehog signaling pathway might undergo a cross-talk with PHC3 in self-renewal of lung cancer stem cells. SFN might be an effective new drug which could inhibit self-renewal of lung cancer stem cells through the modulation of Sonic Hedgehog signaling pathways and PHC3. This study could provide a novel way to improve therapeutic efficacy for lung cancer stem cells.
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Iahtisham-Ul-Haq, Khan S, Awan KA, Iqbal MJ. Sulforaphane as a potential remedy against cancer: Comprehensive mechanistic review. J Food Biochem 2021; 46:e13886. [PMID: 34350614 DOI: 10.1111/jfbc.13886] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 06/30/2021] [Accepted: 07/14/2021] [Indexed: 12/21/2022]
Abstract
Sulforaphane belongs to the active class of isothiocyanates capable of delivering various biological benefits for health promotion and disease prevention. This compound is considered vital to curtail numerous metabolic disorders. Various studies have proven its beneficial effects against cancer prevention and its possible utilization as a therapeutic agent in cancer treatment. Understanding the mechanistic pathways and possible interactions at cellular and subcellular levels is key to design and develop cancer therapeutics for humans. In this respect, a number of mechanisms such as modulation of carcinogen metabolism & phase II enzymatic activities, cell cycle arrest, activation of Nrf2, cytotoxic, proapoptotic and apoptotic pathways have been reported to be involved in cancer prevention. This article provides sufficient information by critical analysis to understand the mechanisms involved in cancer prevention attributed to sulforaphane. Furthermore, various clinical studies have also been included for design and development of novel therapies for cancer prevention and cure. PRACTICAL APPLICATIONS: Diet and dietary components are potential tools to address various lifestyle-related disorders. Due to plenty of environmental and cellular toxicants, the chances of cancer prevalence are quite large which are worsen by adopting unhealthy lifestyles. Cancer can be treated with various therapies but those are acquiring side effects causing the patients to suffer the treatment regime. Nutraceuticals and functional foods provide safer options to prevent or delay the onset of cancer. In this regard, sulforaphane is a pivotal compound to be targeted as a potential agent for cancer treatment both in preventive and therapeutic regimes. This article provides sufficient evidence via discussing the underlying mechanisms of positive effects of sulforaphane to further the research for developing anticancer drugs that will help assuage this lethal morbidity.
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Affiliation(s)
- Iahtisham-Ul-Haq
- School of Food and Nutrition, Faculty of Allied Health Sciences, Minhaj University, Lahore, Pakistan
| | - Sipper Khan
- Institute of Agricultural Engineering, Tropics and Subtropics Group, University of Hohenheim, Stuttgart, Germany
| | - Kanza Aziz Awan
- Department of Food Science and Technology, Faculty of Life Sciences, University of Central Punjab, Lahore, Pakistan
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Patel H, Joshi J, Raval A, Shah F. Identification of Natural Compounds to Inhibit Sonic Hedgehog Pathway in Oral Cancer. Anticancer Agents Med Chem 2021; 22:905-913. [PMID: 34238174 DOI: 10.2174/1871520621666210708100747] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2021] [Revised: 05/21/2021] [Accepted: 05/30/2021] [Indexed: 11/22/2022]
Abstract
BACKGROUND Conventional treatment resistance remains a significant problem in cancer care. Cancer stem cells might play a major role in treatment resistance, and as a result, basic stem cell pathways are instrumental in cancer. Sonic Hedgehog signaling has not been widely studied in oral cancer, and being one of the major cancer stem cell pathways, targeting it with natural compounds could open many opportunities in the treatment scenario. OBJECTIVE The objective of the study was to identify the role of various natural compounds as an anti-cancer agent for oral cancer by targeting the Hedgehog signaling pathway. METHODS The selection of natural compounds were identified through literature review and NPACT database. The protein (3M1N and 3MXW) and ligand molecules were retrieved through the PDB and PubChem database. To carry out docking experiments, the AutoDock 4.2 program was used to study the interaction between the identified protein and ligand. RESULTS Among the 13 identified natural compounds, the top three were selected based on their binding energy. The higher the binding energy on the negative side, the better the interaction formed between protein and ligand. The natural compound showing best results with 3M1N protein were Butein, Biochanin-A, and Curcumin, whereas, with 3MXW, Zerumbone, Curcumin, and Butein were identified. CONCLUSION The identified natural compounds have shown better binding energy to bind the Hh ligands in the absence/presence of a known Sonic Hedgehog inhibitor. Based on the results, natural compounds can be utilized in the current treatment modality for oral cancer either as an individual anti-cancer agent or in combination with the known Sonic Hedgehog inhibitor to curb the increasing incidence rate. Yet, in-vitro evidence in lab setup is required.
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Affiliation(s)
- Hitarth Patel
- Stem Cell Biology Lab, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Jigna Joshi
- Stem Cell Biology Lab, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Apexa Raval
- Stem Cell Biology Lab, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
| | - Franky Shah
- Stem Cell Biology Lab, Department of Cancer Biology, The Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India
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Hong W, Guo F, Yu N, Ying S, Lou B, Wu J, Gao Y, Ji X, Wang H, Li A, Wang G, Yang G. A Novel Folic Acid Receptor-Targeted Drug Delivery System Based on Curcumin-Loaded β-Cyclodextrin Nanoparticles for Cancer Treatment. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:2843-2855. [PMID: 34234415 PMCID: PMC8255901 DOI: 10.2147/dddt.s320119] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/19/2021] [Accepted: 06/25/2021] [Indexed: 01/30/2023]
Abstract
Purpose A novel folate receptor-targeted β-cyclodextrin (β-CD) drug delivery vehicle was constructed to improve the bioavailability, biosafety, and drug loading capacity of curcumin. Controlled release and targeted delivery was achieved by modifying the nanoparticles with folic acid (FA). Methods Folate-conjugated β-CD-polycaprolactone block copolymers were synthesized and characterized. Curcumin-loaded nanoparticles (FA-Cur-NPs) were structured by self-assembly. The physicochemical properties, stability, release behavior and tumor-targeting ability of the fabricated nanoparticles were studied. Results The average particle size and drug loading of FA-Cur-NPs was 151.8 nm and 20.27%, respectively. Moreover, the FA-Cur-NPs exhibited good stability in vitro for 72 h. The drug release profiles showed that curcumin from FA-Cur-NPs was released significantly faster in a pH 6.4 phosphate buffered solution (PBS) than in pH 7.4, indicating that curcumin can be enriched around the tumor site compared with normal cells. Additionally, the internalization of FA-Cur-NPs was aided by FA receptor-mediated endocytosis, and its cytotoxicity was proportional to the cellular uptake efficiency. Furthermore, in vivo studies confirmed that FA-Cur-NPs exhibited marked accumulation in the tumor site and excellent antitumor activity. Conclusion These findings suggest that FA-Cur-NPs are a promising approach for improving cancer therapy through active targeting and controllable release.
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Affiliation(s)
- Weiyong Hong
- Department of Pharmacy, Taizhou Municipal Hospital, Taizhou, 318000, People's Republic of China.,College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Fangyuan Guo
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Nan Yu
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Sanjun Ying
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Bang Lou
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Jiangqing Wu
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Ying Gao
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Xugang Ji
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
| | - Haiying Wang
- Department of Pharmacy, Taizhou Municipal Hospital, Taizhou, 318000, People's Republic of China
| | - Aiqin Li
- Zhejiang Share Bio-Pharm Co., Ltd, Hangzhou, 310019, People's Republic of China
| | - Guoping Wang
- Zhejiang Dayang Biotech Group Co., Ltd, Hangzhou, 311616, People's Republic of China
| | - Gensheng Yang
- College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou, 310014, People's Republic of China
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Erkisa M, Sariman M, Geyik OG, Geyik CG, Stanojkovic T, Ulukay E. Natural Products as a Promising Therapeutic Strategy to Target Cancer Stem Cells. Curr Med Chem 2021; 29:741-783. [PMID: 34182899 DOI: 10.2174/0929867328666210628131409] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2020] [Revised: 03/02/2021] [Accepted: 03/02/2021] [Indexed: 11/22/2022]
Abstract
Cancer is still a deadly disease, and its treatment desperately needs to be managed in a very sophisticated way through fast-developing novel strategies. Most of the cancer cases eventually develop into recurrencies, for which cancer stem cells (CSCs) are thought to be responsible. They are considered as a subpopulation of all cancer cells of tumor tissue with aberrant regulation of self-renewal, unbalanced proliferation, and cell death properties. Moreover, CSCs show a serious degree of resistance to chemotherapy or radiotherapy and immune surveillance as well. Therefore, new classes of drugs are rushing into the market each year, which makes the cost of therapy increase dramatically. Natural products are also becoming a new research area as a diverse chemical library to suppress CSCs. Some of the products even show promise in this regard. So, the near future could witness the introduction of natural products as a source of new chemotherapy modalities, which may result in the development of novel anticancer drugs. They could also be a reasonably-priced alternative to highly expensive current treatments. Nowadays, considering the effects of natural compounds on targeting surface markers, signaling pathways, apoptosis, and escape from immunosurveillance have been a highly intriguing area in preclinical and clinical research. In this review, we present scientific advances regarding their potential use in the inhibition of CSCs and the mechanisms by which they kill the CSCs.
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Affiliation(s)
- Merve Erkisa
- Molecular Cancer Research Center (ISUMKAM), Istinye University, Istanbul, Turkey
| | - Melda Sariman
- Molecular Cancer Research Center (ISUMKAM), Istinye University, Istanbul, Turkey
| | - Oyku Gonul Geyik
- Molecular Cancer Research Center (ISUMKAM), Istinye University, Istanbul, Turkey
| | - Caner Geyik Geyik
- Molecular Cancer Research Center (ISUMKAM), Istinye University, Istanbul, Turkey
| | - Tatjana Stanojkovic
- Experimental Oncology Deparment, Institute for Oncology and Radiology of Serbia, 11000 Belgrade, Pasterova 14. Serbia
| | - Engin Ulukay
- Molecular Cancer Research Center (ISUMKAM), Istinye University, Istanbul, Turkey
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Su X, Chen S, Lu H, Li H, Qin C. Study on the Inhibitory Effect of Curcumin on GBM and Its Potential Mechanism. DRUG DESIGN DEVELOPMENT AND THERAPY 2021; 15:2769-2781. [PMID: 34234410 PMCID: PMC8253996 DOI: 10.2147/dddt.s306602] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/14/2021] [Accepted: 06/03/2021] [Indexed: 11/23/2022]
Abstract
Background Glioblastoma (GBM) is the most prevalent malignant tumor of the central nervous system (CNS). However, current GBM treatments are ineffective, signifying the great importance of exploring new therapeutic targets. Curcumin has been found to be a natural compound with an anticancer potential. However, its targets and mechanisms in GBM are still unclear. Methods Differentially expressed genes (DEGs) were screened from the GBM dataset in the GEO database and intersected with the target genes of curcumin to select potential target genes. Subsequently, survival analysis was performed with the GEPIA database to confirm the effect of target genes on the prognosis of GBM, and functional enrichment analysis was performed using the DAVID database. In vitro, CCK-8 assay was used to screen the appropriate concentration of curcumin; scratch and transwell invasion assays were used to evaluate the effect of curcumin on the migration and invasion abilities of GBM cells. Furthermore, RT-qPCR and Western blotting were used to detect changes in target genes and flow cytometry was used to assess the apoptosis level. Results A total of 16 target genes of curcumin and GBM were obtained, among which ENO1, MMP2, and PRKD2 significantly affected the prognosis (P < 0.05). We further selected ENO1 for functional enrichment analysis and found that it was enriched in the glycolytic pathway. Meanwhile, in vitro experiments showed that curcumin could inhibit the migration and invasion of U251 cells and promote apoptosis (P < 0.05). Conclusion ENO1 could be a possible target for curcumin in the suppression of GBM cells.
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Affiliation(s)
- Xiaotao Su
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Shaohua Chen
- Department of Urology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Hongyu Lu
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Haoyu Li
- Department of Ophthalmology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
| | - Chao Qin
- Department of Neurology, The First Affiliated Hospital of Guangxi Medical University, Nanning, 530021, People's Republic of China
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Malik P, Hoidal JR, Mukherjee TK. Recent Advances in Curcumin Treated Non-Small Cell Lung Cancers: An Impetus of Pleiotropic Traits and Nanocarrier Aided Delive ry. Curr Med Chem 2021; 28:3061-3106. [PMID: 32838707 DOI: 10.2174/0929867327666200824110332] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2020] [Revised: 07/20/2020] [Accepted: 07/27/2020] [Indexed: 01/10/2023]
Abstract
Characterized by the abysmal 18% five year survival chances, non-small cell lung cancers (NSCLCs) claim more than half of their sufferers within the first year of being diagnosed. Advances in biomedical engineering and molecular characterization have reduced the NSCLC diagnosis via timid screening of altered gene expressions and impaired cellular responses. While targeted chemotherapy remains a major option for NSCLCs complications, delayed diagnosis, and concurrent multi-drug resistance remain potent hurdles in regaining normalcy, ultimately resulting in relapse. Curcumin administration presents a benign resolve herein, via simultaneous interception of distinctly expressed pathological markers through its pleiotropic attributes and enhanced tumor cell internalization of chemotherapeutic drugs. Studies on NSCLC cell lines and related xenograft models have revealed a consistent decline in tumor progression owing to enhanced chemotherapeutics cellular internalization via co-delivery with curcumin. This presents an optimum readiness for screening the corresponding effectiveness in clinical subjects. Curcumin is delivered to NSCLC cells either (i) alone, (ii) in stoichiometrically optimal combination with chemotherapeutic drugs, (iii) through nanocarriers, and (iv) nanocarrier co-delivered curcumin and chemotherapeutic drugs. Nanocarriers protect the encapsulated drug from accidental and non-specific spillage. A unanimous trait of all nanocarriers is their moderate drug-interactions, whereby native structural expressions are not tampered. With such insights, this article focuses on the implicit NSCLC curative mechanisms viz-a-viz, free curcumin, nanocarrier delivered curcumin, curcumin + chemotherapeutic drug and nanocarrier assisted curcumin + chemotherapeutic drug delivery.
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Affiliation(s)
- Parth Malik
- School of Chemical Sciences, Central University of Gujarat, Gandhinagar, India
| | - John R Hoidal
- Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah, Salt Lake City, Utah, United States
| | - Tapan K Mukherjee
- Division of Respiratory, Critical Care and Occupational Pulmonary Medicine, University of Utah, Salt Lake City, Utah, United States
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Wu Y, Wang T, Xia L, Zhang M. LncRNA WDFY3-AS2 promotes cisplatin resistance and the cancer stem cell in ovarian cancer by regulating hsa-miR-139-5p/SDC4 axis. Cancer Cell Int 2021; 21:284. [PMID: 34051810 PMCID: PMC8164817 DOI: 10.1186/s12935-021-01993-x] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 05/24/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Ovarian cancer (OC) is a high-mortality gynecological cancer that is typically treated with cisplatin, although such treatment often results in chemoresistance. Ovarian cancer resistance is usually related to cell stemness. Herein, we explored the function of lncRNA WDFY3-AS2 in OC cell resistance to cisplatin (DDP). METHODS Cisplatin resistant OC A2780 cell lines (A2780-DDP) were established by long-term exposure to cisplatin. CCK-8 assay were performed to evaluate the viability of A2780, and A2780-DDP cells. Quantitative RT-PCR was used to examine the expression of lncRNA WDFY3-AS2, miR-139-5p, and SDC4 in A2780-DDP cell lines. After treatment with cisplatin, cell apoptosis and CD44+CD166+-positive cells were measured by flow cytometry. The transwell assays were employed to measure the effect of WDFY3-AS2 on cell migration, and invasion. In addition, tumorsphere formation assay was used to enrich OC cancer stem cells (CSCs) from A2780-DDP cells. The expression of CSC markers (SOX2, OCT4, and Nanog) was detected by western blotting. The regulatory mechanism was confirmed by RNA pull down, and luciferase reporter assays. Furthermore, xenograft tumor in nude mice was used to assess the impact of WDFY3-AS2 on cisplatin resistance in OC in vivo. RESULTS WDFY3-AS2 was highly expressed in OC A2780-DDP cells, and silencing WDFY3-AS2 significantly inhibited proliferation, migration and invasion but increased apoptosis in OC A2780-DDP cells. Additionally, WDFY3-AS2 significantly promoted the A2780-DDP cells tumorspheres. WDFY3-AS2 was predicted to impact OC by sponging miR-139-5p and regulating SDC4. The xenografts inoculated with A2780-DDP cells additionally confirmed that tumor growth in vivo was reduced by si-WDFY3-AS2 transfection. MiR-139-5p inhibitor or SDC4 overexpression could restore the suppressive influence of silenced WDFY3-AS2 on tumor growth. CONCLUSIONS Together, WDFY3-AS2 may lead to change of cisplatin resistance by the expression of miR-139-5p/SDC4 in the OC A2870-DDP cells both in vitro and in vivo. Our finding may provide a drug target for the drug resistance of OC.
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Affiliation(s)
- Yue Wu
- Department of Integrated Chinese and Western Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Hefei, 230022, Anhui, China
- The Traditional and Western Medicine (TCM)-Integrated Cancer Center of Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Ting Wang
- Department of Integrated Chinese and Western Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Hefei, 230022, Anhui, China
- The Traditional and Western Medicine (TCM)-Integrated Cancer Center of Anhui Medical University, 81 Meishan Road, Hefei, 230032, China
| | - Lin Xia
- Graduate School of Anhui, University of Traditional Chinese Medicine, Hefei, 230012, Anhui, China
| | - Mei Zhang
- Department of Integrated Chinese and Western Medicine Oncology, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Hefei, 230022, Anhui, China.
- The Traditional and Western Medicine (TCM)-Integrated Cancer Center of Anhui Medical University, 81 Meishan Road, Hefei, 230032, China.
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Heng WS, Kruyt FAE, Cheah SC. Understanding Lung Carcinogenesis from a Morphostatic Perspective: Prevention and Therapeutic Potential of Phytochemicals for Targeting Cancer Stem Cells. Int J Mol Sci 2021; 22:ijms22115697. [PMID: 34071790 PMCID: PMC8198077 DOI: 10.3390/ijms22115697] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 05/06/2021] [Accepted: 05/07/2021] [Indexed: 12/24/2022] Open
Abstract
Lung cancer is still one of the deadliest cancers, with over two million incidences annually. Prevention is regarded as the most efficient way to reduce both the incidence and death figures. Nevertheless, treatment should still be improved, particularly in addressing therapeutic resistance due to cancer stem cells—the assumed drivers of tumor initiation and progression. Phytochemicals in plant-based diets are thought to contribute substantially to lung cancer prevention and may be efficacious for targeting lung cancer stem cells. In this review, we collect recent literature on lung homeostasis, carcinogenesis, and phytochemicals studied in lung cancers. We provide a comprehensive overview of how normal lung tissue operates and relate it with lung carcinogenesis to redefine better targets for lung cancer stem cells. Nine well-studied phytochemical compounds, namely curcumin, resveratrol, quercetin, epigallocatechin-3-gallate, luteolin, sulforaphane, berberine, genistein, and capsaicin, are discussed in terms of their chemopreventive and anticancer mechanisms in lung cancer and potential use in the clinic. How the use of phytochemicals can be improved by structural manipulations, targeted delivery, concentration adjustments, and combinatorial treatments is also highlighted. We propose that lung carcinomas should be treated differently based on their respective cellular origins. Targeting quiescence-inducing, inflammation-dampening, or reactive oxygen species-balancing pathways appears particularly interesting.
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Affiliation(s)
- Win Sen Heng
- Faculty of Medical Sciences, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (W.S.H.); (F.A.E.K.)
- Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
| | - Frank A. E. Kruyt
- Faculty of Medical Sciences, University Medical Center Groningen, 9713 GZ Groningen, The Netherlands; (W.S.H.); (F.A.E.K.)
| | - Shiau-Chuen Cheah
- Faculty of Medicine and Health Sciences, UCSI University, Kuala Lumpur 56000, Malaysia
- Correspondence: ; Tel.: +60-3-91018880
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