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Sah SK, Ajay SA, Donadkar AD, Kamath AJ, Devan AR, Soman R, Kumar AR, Unni AR, Sithara MS, Sudheesh MS, Nath LR. Ternary complex of Kaempferol-Hydroxypropyl-β-Cyclodextrin-Liposomes against hepatocellular carcinoma: Preparation, validation, pharmacokinetics and efficacy studies. Int J Pharm 2025; 671:125261. [PMID: 39855283 DOI: 10.1016/j.ijpharm.2025.125261] [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: 11/19/2024] [Revised: 01/20/2025] [Accepted: 01/21/2025] [Indexed: 01/27/2025]
Abstract
Kaempferol (KP), a GRAS-certified phytomolecule enrolled in Phase I trials, is reported with various biological effects including anticancer activity. However, its poor pharmacokinetic profile limits the translational utility. Studies indicate that liposomes incorporating cyclodextrin inclusion complexes improves the bioavailability of hydrophobic drugs. The present study focuses on preparing and validating a novel ternary complex of Kaempferol-Hydroxypropyl-β-Cyclodextrin-Liposomes (KP-HP-β-CD-Liposomes) that shows a particle size of 131.70 ± 0.10 nm, a zeta potential of -26.59 ± 0.42 mV, and a drug entrapment efficiency of 90.14 ± 0.25 %. The KP-HP-β-CD-Liposomes demonstrate stability under refrigerated conditions (2-8 °C) over a three-month period. Also, it doesn't exhibit any cytotoxicity in normal fibroblast cells even up to 48 mg/ml while it produces a dose dependent cytotoxicity in HepG2 cells. It shows a better cellular uptake in HepG2 cells in comparison with pure Kaempferol as evidenced by HPLC analysis. KP-HP-β-CD-Liposomes induce apoptosis in HepG2 cells as assessed by Acridine orange ethidium bromide staining. Pharmacokinetic studies on Sprague Dawley rats indicate a significant improvement in Cmax and AUC(0-∞) of Kaempferol. The tissue distribution studies show that KP-HP-β-CD-Liposomes are highly accumulated in liver. The KP-HP-β- CD-Liposomes inhibits the development of hepatic tumors in Syngeneic N1S1 animal models.
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Affiliation(s)
- Sunil Kumar Sah
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India; Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - S A Ajay
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India; Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - Asawari Dilip Donadkar
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India; Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - Adithya Jayaprakash Kamath
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India; Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - Aswathy R Devan
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India; Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - Rahul Soman
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - Ayana R Kumar
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India; Department of Pharmacology, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - Ashok R Unni
- Central Lab Animal Facility, Department of Veterinary Medicine, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - M S Sithara
- Central Lab Animal Facility, Department of Veterinary Medicine, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - M S Sudheesh
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India
| | - Lekshmi R Nath
- Department of Pharmacognosy, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Science Campus, Kochi 682041 Kerala, India.
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2
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Alshahrani MM. Advancements in Pyrazine Derivatives as Anticancer Agents: A Comprehensive Review (2010-2024). Anticancer Agents Med Chem 2025; 25:151-163. [PMID: 39318219 DOI: 10.2174/0118715206333399240912071555] [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: 05/26/2024] [Revised: 08/28/2024] [Accepted: 09/02/2024] [Indexed: 09/26/2024]
Abstract
Cancer, an intricate and formidable disease, continues to challenge Medical Science with its diverse manifestations and relentless progression. In the pursuit of novel therapeutic strategies, organic heterocyclic compounds have emerged as promising candidates due to their versatile chemical structures and intricate interactions with biological systems. Among these, pyrazine derivatives are characterized by a six-membered aromatic ring containing four carbon and two nitrogen atoms situated in a 1,4-orientation. These compounds garnered significant attention for their potential as anticancer agents. This comprehensive review provides a detailed analysis of the advancements made during this timeframe, encompassing the chemical diversity of pyrazine derivatives, their mechanisms of action at the cellular level, and structure-activity relationships, spanning the years 2010 to 2024. By examining their therapeutic potential, challenges, and future prospects, this review offers valuable insights into the evolving landscape of pyrazine derivatives as potent tools in the fight against cancer.
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Affiliation(s)
- Mohammed Merae Alshahrani
- Department of Clinical Laboratory Sciences, Faculty of Applied Medical Sciences, Najran University, 1988, Najran, 61441, Saudi Arabia
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3
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Guo X, Wang F, Li X, Luo Q, Liu B, Yuan J. Mitochondrial cholesterol metabolism related gene model predicts prognosis and treatment response in hepatocellular carcinoma. Transl Cancer Res 2024; 13:6623-6644. [PMID: 39816559 PMCID: PMC11730194 DOI: 10.21037/tcr-24-1153] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/06/2024] [Accepted: 10/25/2024] [Indexed: 01/18/2025]
Abstract
Background The persistently high mortality and morbidity rates of hepatocellular carcinoma (HCC) remain a global concern. Notably, the disruptions in mitochondrial cholesterol metabolism (MCM) play a pivotal role in the progression and development of HCC, underscoring the significance of this metabolic pathway in the disease's etiology. The purpose of this research was to investigate genes associated with MCM and develop a model for predicting the prognostic features of patients with HCC. Methods MCM-related genes (MCMGs) were identified through The Cancer Genome Atlas (TCGA), The Molecular Signatures Database (MsigDB), and the Mitocarta3.0 databases. Differential gene expression analysis and least absolute shrinkage and selection operator (LASSO) Cox regression analysis were performed using R software to construct a MCM-related model. This model underwent further analysis for somatic mutations, single sample gene set enrichment analysis (ssGSEA), stromal and immune cell estimation, immune checkpoint evaluation, and drug susceptibility prediction to assess the tumor microenvironment (TME) and therapeutic responses. The mRNA expression levels of the genes associated with the model were quantified using real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). Results The model, which included six MCMGs (ACADL, ACLY, TXNRD1, DTYMK, ACAT1, and FLAD1), divided all patients (age ≤65 vs. >65 years, P<0.001; male vs. female, ns) into a high-risk group and a low-risk group. The high-risk group showed a higher mortality rate and lower survival rate with AUC of 0.785, 0.752, 0.756, 0.774 and 0.759 for the 1-, 2-, 3-, 4-, and 5-year respectively. A nomogram based on risk score, stage, T, and M had a better prognostic accuracy, with AUC of 0.808, 0.796, 0.811, 0.824 and 0.795 for the 1-, 2-, 3-, 4-, and 5-year respectively. The high-risk group showed enrichment in cell cycle, cell division, and chromosome processes, and a significantly higher tumor mutation burden (TMB) value compared to the low-risk group. Further immune infiltration analysis indicated a significantly reduction in the abundances of some immune cells (activated CD4 T cells, type 2 helper T cells, and neutrophils) and significantly higher expression levels of some immune checkpoint (CD80, CTLA4, HAVCR2, and TNFRSF4) in the high-risk group. Moreover, the risk score was associated with the response to immune checkpoint inhibitors (ICIs) therapy and efficiencies of multiple chemotherapy drugs. Conclusions This study developed a prognostic model based on MCMGs, which can predict the prognosis of liver cancer patients and their response to immunotherapy and chemotherapy. The model may provide new strategies to enhance the prognosis and treatment of HCC.
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Affiliation(s)
- Xuna Guo
- Department of Biomedical Engineering, School of Life Sciences, Guangxi Medical University, Nanning, China
| | - Feng Wang
- Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Xuejing Li
- Department of Physiology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Qiuqian Luo
- Department of Physiology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
| | - Bihan Liu
- Department of Biomedical Engineering, School of Life Sciences, Guangxi Medical University, Nanning, China
| | - Jianhui Yuan
- Department of Biomedical Engineering, School of Life Sciences, Guangxi Medical University, Nanning, China
- Department of Physiology, School of Basic Medical Sciences, Guangxi Medical University, Nanning, China
- Department of Physics, Guangxi Medical University, Nanning, China
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4
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AbouSamra MM. Liposomal nano-carriers mediated targeting of liver disorders: mechanisms and applications. J Liposome Res 2024; 34:728-743. [PMID: 38988127 DOI: 10.1080/08982104.2024.2377085] [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: 04/18/2024] [Revised: 06/12/2024] [Accepted: 07/02/2024] [Indexed: 07/12/2024]
Abstract
Liver disorders present a significant global health challenge, necessitating the exploration of innovative treatment modalities. Liposomal nanocarriers have emerged as promising candidates for targeted drug delivery to the liver. This review offers a comprehensive examination of the mechanisms and applications of liposomal nanocarriers in addressing various liver disorders. Firstly discussing the liver disorders and the conventional treatment approaches, the review delves into the liposomal structure and composition. Moreover, it tackles the different mechanisms of liposomal targeting including both passive and active strategies. After that, the review moves on to explore the therapeutic potentials of liposomal nanocarriers in treating liver cirrhosis, fibrosis, viral hepatitis, and hepatocellular carcinoma. Through discussing recent advancements and envisioning future perspectives, this review highlights the role of liposomal nanocarriers in enhancing the effectiveness and the safety of liver disorders and consequently improving patient outcomes and enhances life quality.
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Affiliation(s)
- Mona M AbouSamra
- Pharmaceutical Technology Department, National Research Centre, Giza, Egypt
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5
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Xu X, Wu S, Zhang Y, Fan W, Lin X, Chen K, Lin X. m6A modification of VEGFA mRNA by RBM15/YTHDF2/IGF2BP3 contributes to angiogenesis of hepatocellular carcinoma. Mol Carcinog 2024; 63:2174-2189. [PMID: 39092767 DOI: 10.1002/mc.23802] [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: 12/18/2023] [Revised: 07/19/2024] [Accepted: 07/24/2024] [Indexed: 08/04/2024]
Abstract
Vascular endothelial growth factor A (VEGFA) plays a critical role as a potent angiogenesis factor and is highly expressed in hepatocellular carcinoma (HCC). Although the expression of VEGFA has been strongly linked to the aggressive nature of HCC, the specific posttranscriptional modifications that might contribute to VEGFA expression and HCC angiogenesis are not yet well understood. In this study, we aimed to investigate the epitranscriptome regulation of VEGFA in HCC. A comprehensive analysis integrating MeRIP-seq, RNA-seq, and crosslinking-immunprecipitation-seq data revealed that VEGFA was hypermethylated in HCC and identified the potential m6A regulators of VEGFA including a m6A methyltransferase complex component RBM15 and the two readers, YTHDF2 and IGF2BP3. Through rigorous cell and molecular biology experiments, RBM15 was validated as a key component of methyltransferase complex responsible for m6A methylation of VEGFA, which was subsequently recognized and stabilized by IGF2BP3 and YTHDF2, leading to enhanced VEGFA expression and VEGFA-related functions such as human umbilical vascular endothelial cells (HUVEC) migration and tube formation. In the HCC xenograft model, knockdown of RBM15, IGF2BP3, or YTHDF2 resulted in reduced expression of VEGFA, accompanied by significant inhibition of tumor growth closely associated with VEGFA expression and angiogenesis. Furthermore, our analysis of HCC clinical samples identified positive correlations between the expression levels of VEGFA and the regulators RBM15, IGF2BP3, and YTHDF2. Collectively, these findings offer novel insights into the posttranscriptional modulation of VEGFA and provide potential avenues for alternative approaches to antiangiogenesis therapy targeting VEGFA.
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MESH Headings
- Humans
- Carcinoma, Hepatocellular/genetics
- Carcinoma, Hepatocellular/pathology
- Carcinoma, Hepatocellular/metabolism
- RNA-Binding Proteins/genetics
- RNA-Binding Proteins/metabolism
- Liver Neoplasms/genetics
- Liver Neoplasms/pathology
- Liver Neoplasms/metabolism
- Vascular Endothelial Growth Factor A/genetics
- Vascular Endothelial Growth Factor A/metabolism
- Animals
- Neovascularization, Pathologic/genetics
- Neovascularization, Pathologic/metabolism
- Neovascularization, Pathologic/pathology
- Mice
- RNA, Messenger/genetics
- Gene Expression Regulation, Neoplastic
- Human Umbilical Vein Endothelial Cells
- Mice, Nude
- Cell Line, Tumor
- Adenosine/metabolism
- Adenosine/genetics
- Adenosine/analogs & derivatives
- Cell Proliferation/genetics
- Mice, Inbred BALB C
- Xenograft Model Antitumor Assays
- Male
- Cell Movement/genetics
- Angiogenesis
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Affiliation(s)
- Xiaoxin Xu
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fuzhou, China
| | - Shuxiang Wu
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fuzhou, China
| | - Yi Zhang
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fuzhou, China
| | - Weijie Fan
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fuzhou, China
| | - Xinjian Lin
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fuzhou, China
| | - Kunqi Chen
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fuzhou, China
| | - Xu Lin
- Key Laboratory of Gastrointestinal Cancer (Fujian Medical University), Ministry of Education, School of Basic Medical Sciences, Fuzhou, China
- Department of Medical Microbiology, Fujian Key Laboratory of Tumor Microbiology, School of Basic Medical Sciences, Fujian Medical University, Fuzhou, China
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6
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Manickasamy MK, Kumar A, BharathwajChetty B, Alqahtani MS, Abbas M, Alqahtani A, Unnikrishnan J, Bishayee A, Sethi G, Kunnumakkara AB. Synergistic enhancement: Exploring the potential of piperine in cancer therapeutics through chemosensitization and combination therapies. Life Sci 2024; 354:122943. [PMID: 39117139 DOI: 10.1016/j.lfs.2024.122943] [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: 05/12/2024] [Revised: 07/15/2024] [Accepted: 08/04/2024] [Indexed: 08/10/2024]
Abstract
Despite significant advancements in chemotherapy, effective treatments for advanced cancer stages remain largely elusive due to chemoresistance. Resistance to anticancer agents in cancer cells can arise through various mechanisms, including multi-drug resistance, inhibition of apoptosis, modification of drug targets, and enhancement of DNA repair capabilities. Consequently, there is a critical need for agents that can suppress the molecular signatures responsible for drug resistance. Piperine, an active alkaloid extracted from Piper nigrum L. (black pepper), is one such agent that has been extensively studied for its potential in addressing chronic diseases, including cancer. Piperine's antineoplastic properties are mediated through the regulation of numerous key cellular signaling pathways and the modulation of various biological processes. Its capability to enhance drug bioavailability and counteract mechanisms of drug resistance, such as the inhibition of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP-1), emphasizes its potential as an adjunct in cancer therapy. Research across various cancer types has demonstrated piperine's role in chemosensitization by targeting P-gp and MRP-1 and altering drug-metabolizing enzymes. This review provides a comprehensive analysis of piperine's pharmacological characteristics and its capacity to modulate several cellular signaling pathways involved in drug resistance. Furthermore, the review emphasizes how piperine, when used in conjunction with other chemotherapeutic agents or natural compounds, can enhance therapeutic effects, leading to improved outcomes in cancer treatment.
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Affiliation(s)
- Mukesh Kumar Manickasamy
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati 781 039, Assam, India
| | - Aviral Kumar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati 781 039, Assam, India
| | - Bandari BharathwajChetty
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati 781 039, Assam, India
| | - Mohammed S Alqahtani
- Radiological Sciences Department, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia
| | - Mohamed Abbas
- Electrical Engineering Department, College of Engineering, King Khalid University, Abha 61421, Saudi Arabia
| | - Athba Alqahtani
- Research Centre, King Fahad Medical City, Riyadh 11525, Saudi Arabia
| | - Jyothsna Unnikrishnan
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati 781 039, Assam, India
| | - Anupam Bishayee
- Department of Pharmacology, College of Osteopathic Medicine, Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, United States of America
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117600.
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati 781 039, Assam, India.
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Moar K, Yadav S, Pant A, Deepika, Maurya PK. Anti-tumor Effects of Polyphenols via Targeting Cancer Driving Signaling Pathways: A Review. Indian J Clin Biochem 2024; 39:470-488. [PMID: 39346722 PMCID: PMC11436542 DOI: 10.1007/s12291-024-01222-y] [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: 02/09/2024] [Accepted: 04/02/2024] [Indexed: 10/01/2024]
Abstract
The use of drugs in chemotherapy poses numerous side effects. Hence the use of natural substances that can help in the prevention and cure of the disease is a dire necessity. Cancer is a deadly illness and combination of diseases, the menace of which is rising with every passing year. The research community and scientists from all over the world are working towards finding a cure of the disease. The use of polyphenols which are naturally derived from plants have a great potential to be used as anti-cancer drugs and also the use of fruits and vegetables which are rich in these polyphenols can also help in the prevention of diseases. The study aims to compile the available literature and research studies on the anti-cancer effects of polyphenols and the signaling pathways that are affected by them. To review the anti-cancer effects of polyphenols, Google Scholar, PubMed and ScienceDirect were used to study the literature available. The article that have been used for literature review were filtered using keywords including cancer, polyphenols and signaling pathways. Majorly articles from the last 10 years have been considered for the review but relevant articles from earlier than 10 years have also been considered. Almost 400 articles were studied for the review and 200 articles have been cited. The current review shows the potential of polyphenols as anti-cancer compounds and how the consumption of a diet rich in polyphenols can help in the prevention of cancer. Because of their capacity to affect a variety of oncogenic and oncosuppressive signaling pathways, phytochemicals derived from plants have been effectively introduced as an alternative anticarcinogenic medicines. Graphical Abstract
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Affiliation(s)
- Kareena Moar
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
| | - Somu Yadav
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
| | - Anuja Pant
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
| | - Deepika
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
| | - Pawan Kumar Maurya
- Department of Biochemistry, Central University of Haryana, Mahendergarh, 123031 India
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8
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Bhat AA, Afzal M, Moglad E, Thapa R, Ali H, Almalki WH, Kazmi I, Alzarea SI, Gupta G, Subramaniyan V. lncRNAs as prognostic markers and therapeutic targets in cuproptosis-mediated cancer. Clin Exp Med 2024; 24:226. [PMID: 39325172 PMCID: PMC11427524 DOI: 10.1007/s10238-024-01491-0] [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: 08/11/2024] [Accepted: 09/16/2024] [Indexed: 09/27/2024]
Abstract
Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, including cancer progression and stress response. Recent studies have demonstrated that copper accumulation induces a unique form of cell death known as cuproptosis, with lncRNAs playing a key role in regulating cuproptosis-associated pathways. These lncRNAs may trigger cell-specific responses to copper stress, presenting new opportunities as prognostic markers and therapeutic targets. This paper delves into the role of lncRNAs in cuproptosis-mediated cancer, underscoring their potential as biomarkers and targets for innovative therapeutic strategies. A thorough review of scientific literature was conducted, utilizing databases such as PubMed, Google Scholar, and ScienceDirect, with search terms like 'lncRNAs,' 'cuproptosis,' and 'cancer.' Studies were selected based on their relevance to lncRNA regulation of cuproptosis pathways and their implications for cancer prognosis and treatment. The review highlights the significant contribution of lncRNAs in regulating cuproptosis-related genes and pathways, impacting copper metabolism, mitochondrial stress responses, and apoptotic signaling. Specific lncRNAs are potential prognostic markers in breast, lung, liver, ovarian, pancreatic, and gastric cancers. The objective of this article is to explore the role of lncRNAs as potential prognostic markers and therapeutic targets in cancers mediated by cuproptosis.
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Affiliation(s)
- Asif Ahmad Bhat
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Muhammad Afzal
- Department of Pharmaceutical Sciences, Pharmacy Program, Batterjee Medical College, P.O. Box 6231, 21442, Jeddah, Saudi Arabia
| | - Ehssan Moglad
- Department of Pharmaceutics, College of Pharmacy, Prince Sattam Bin Abdulaziz University, 11942, Al Kharj, Saudi Arabia
| | - Riya Thapa
- Uttaranchal Institute of Pharmaceutical Sciences, Uttaranchal University, Dehradun, India
| | - Haider Ali
- Centre for Global Health Research, Saveetha Medical College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
- Department of Pharmacology, Kyrgyz State Medical College, Bishkek, Kyrgyzstan
| | - Waleed Hassan Almalki
- Department of Pharmacology, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University, 21589, Jeddah, Saudi Arabia
| | - Sami I Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, 72341, Sakaka, Aljouf, Saudi Arabia
| | - Gaurav Gupta
- Centre for Research Impact & Outcome, Chitkara College of Pharmacy, Chitkara University, Rajpura, Punjab, 140401, India
- Centre of Medical and Bio-Allied Health Sciences Research, Ajman University, Ajman, United Arab Emirates
| | - Vetriselvan Subramaniyan
- Pharmacology Unit, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Jalan Lagoon Selatan, 47500, Bandar Sunway, Selangor Darul Ehsan, Malaysia.
- Department of Medical Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia.
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9
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Roney M, Issahaku AR, Tufail N, Wilhelm A, Aluwi MFFM. Computational Screening of FDA‐Approved Hepatitis C Drugs for Inhibition of VEGFR2 in Liver Cancer. ChemistrySelect 2024; 9. [DOI: 10.1002/slct.202402683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/04/2024] [Accepted: 07/25/2024] [Indexed: 01/05/2025]
Abstract
AbstractLiver cancer (LC) is one of the most common tumours and the leading cause of cancer‐related death globally. Amidst the problems associated with existing treatments, such as hepatotoxicity, recurrence, drug resistance, and other adverse effects, researchers are under pressure to find alternatives. Towards a comprehensive rationalisation of the search for new anti‐LC drugs among approved ones, we employed an in‐silico approach to accelerate the selection of the most efficacious LC drugs. The FDA‐approved hepatitis C virus (HCV) drugs were docked with the LC protein using the AutoDock Vina software. Compared to the control compound, two FDA‐approved HCV drugs (DB09102 and DB09027) were selected based on their binding energies and interactions with the target protein, which showed comparable binding energies. Furthermore, these compounds were then subjected to molecular dynamic simulation, principle component analysis, and MMGBSA using the AMBER20 software, and the results showed stable complexes compared to the control complex. All things considered, this study will help the scientific community and society find a novel drug to treat LC.
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Affiliation(s)
- Miah Roney
- Faculty of Industrial Sciences and Technology Universiti Malaysia Pahang Al-Sultan Abdullah Lebuhraya Persiaran Tun Khalil Yaakob Kuantan, Pahang Malaysia
- Centre for Bio-aromatic Research Universiti Malaysia Pahang Al-Sultan Abdullah Lebuhraya Persiaran Tun Khalil Yaakob Kuantan, Pahang Malaysia
| | - Abdul Rashid Issahaku
- Department of Chemistry University of the Free State 205 Nelson Mandela Avenue 9301 Bloemfontein South Africa
| | - Nasir Tufail
- C.M.P. Degree College University of Allahabad 211002 Uttar Pradesh India
| | - Anke Wilhelm
- Department of Chemistry University of the Free State 205 Nelson Mandela Avenue 9301 Bloemfontein South Africa
| | - Mohd Fadhlizil Fasihi Mohd Aluwi
- Faculty of Industrial Sciences and Technology Universiti Malaysia Pahang Al-Sultan Abdullah Lebuhraya Persiaran Tun Khalil Yaakob Kuantan, Pahang Malaysia
- Centre for Bio-aromatic Research Universiti Malaysia Pahang Al-Sultan Abdullah Lebuhraya Persiaran Tun Khalil Yaakob Kuantan, Pahang Malaysia
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10
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DJALDETTI MEIR. Immunomodulatory and chemopreventive effects of resveratrol on the digestive system cancers. Oncol Res 2024; 32:1389-1399. [PMID: 39220125 PMCID: PMC11361903 DOI: 10.32604/or.2024.049745] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2024] [Accepted: 05/23/2024] [Indexed: 09/04/2024] Open
Abstract
Resveratrol (RSV), the primary polyphenol found in grapes, has been revealed to have anti-inflammatory properties by reducing the capacity of the peripheral blood mononuclear cells to produce pro-inflammatory cytokines, including IL-1β, IL-6, IL-1ra and TNFα. Considering the close association between chronic inflammation and cancer development, RSV's immunomodulatory properties are one way by which the polyphenol may inhibit cancer initiation, proliferation, neovascularization, and migration. Resveratrol influences the generation of microtumor environment which is one of the key factors in cancer progress. In addition to immunomodulation, RSV inhibits cancer development by expressing anti-oxidant effects, causing cell cycle arrest, stimulating the function of certain enzymes, and activating cell signaling pathways. The end outcome is one of the various forms of cell death, including apoptosis, pyroptosis, necroptosis, and more, as it has been observed in vitro. RSV has been shown to act against cancer in practically every organ, while its effects on colon cancer have been documented more frequently. It is remarkable that longer-term clinical studies that may have established the potential for this natural substance to serve as a therapeutic adjuvant to traditional anti-cancer medications were not prompted by the encouraging outcomes seen with cancer cells treated with non-toxic doses of resveratrol. The current review aims to assess the recent findings about the immunological and anti-cancer characteristics of RSV, with a particular emphasis on cancers of the digestive tract, as a challenge for future clinical research that may contribute to the better prognosis of cancer.
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Affiliation(s)
- MEIR DJALDETTI
- />Laboratory for Immunology and Hematology Research, Rabin Medical Center, Hasharon Hospital, Petah-Tiqva, the Sackler School of Medicine, Tel-Aviv University, Ramat Aviv, 69978, Israel
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11
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Rahman MA, Rakib-Uz-Zaman SM, Chakraborti S, Bhajan SK, Gupta RD, Jalouli M, Parvez MAK, Shaikh MH, Hoque Apu E, Harrath AH, Moon S, Kim B. Advancements in Utilizing Natural Compounds for Modulating Autophagy in Liver Cancer: Molecular Mechanisms and Therapeutic Targets. Cells 2024; 13:1186. [PMID: 39056768 PMCID: PMC11274515 DOI: 10.3390/cells13141186] [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: 04/16/2024] [Revised: 06/30/2024] [Accepted: 07/04/2024] [Indexed: 07/28/2024] Open
Abstract
Autophagy, an intrinsic catabolic mechanism that eliminates misfolded proteins, dysfunctional organelles, and lipid droplets, plays a vital function in energy balance and cytoplasmic quality control, in addition to maintaining cellular homeostasis. Liver cancer such as hepatocellular carcinoma (HCC) is one of the most common causes of cancer deaths globally and shows resistance to several anticancer drugs. Despite the rising incidence and poor prognosis of malignant HCC, the underlying molecular mechanisms driving this aggressive cancer remain unclear. Several natural compounds, such as phytochemicals of dietary and non-dietary origin, affect hepatocarcinogenesis signaling pathways in vitro and in vivo, which may help prevent and treat HCC cells. Current HCC cells treatments include chemotherapy, radiation, and surgery. However, these standard therapies have substantial side effects, and combination therapy enhances side effects for an acceptable therapeutic benefit. Therefore, there is a need to develop treatment strategies for HCC cells that are more efficacious and have fewer adverse effects. Multiple genetic and epigenetic factors are responsible for the HCC cells to become resistant to standard treatment. Autophagy contributes to maintain cellular homeostasis, which activates autophagy for biosynthesis and mitochondrial regulation and recycling. Therefore, modifying autophagic signaling would present a promising opportunity to identify novel therapies to treat HCC cells resistant to current standard treatments. This comprehensive review illustrates how natural compounds demonstrate their anti-hepatocellular carcinoma function through autophagy.
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Affiliation(s)
- Md Ataur Rahman
- Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA;
| | - S M Rakib-Uz-Zaman
- Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA; (S.M.R.-U.-Z.); (S.C.)
- Biotechnology Program, Department of Mathematics and Natural Sciences, School of Data and Sciences, BRAC University, Dhaka 1212, Bangladesh
| | - Somdeepa Chakraborti
- Department of Biological Sciences, University of Delaware, Newark, DE 19716, USA; (S.M.R.-U.-Z.); (S.C.)
| | - Sujay Kumar Bhajan
- Department of Biotechnology & Genetic Engineering, Bangabandhu Sheikh Mujibur Rahman Science & Technology University, Gopalganj 8100, Bangladesh;
| | - Rajat Das Gupta
- Department of Epidemiology and Biostatistics, Arnold School of Public Health, University of South Carolina, Columbia, SC 29208, USA;
| | - Maroua Jalouli
- Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh 11623, Saudi Arabia;
| | | | - Mushfiq H. Shaikh
- Department of Otolaryngology-Head & Neck Surgery, Western University, London, ON N6A 4V2, Canada;
| | - Ehsanul Hoque Apu
- Department of Biomedical Sciences, College of Dental Medicine, Lincoln Memorial University, Knoxville, TN 37923, USA;
- DeBusk College of Osteopathic Medicine, Lincoln Memorial University, Harrogate, TN 37752, USA
- Division of Hematology and Oncology, Department of Internal Medicine, Michigan Medicine, University of Michigan, Ann Arbor, MI 48109, USA
| | - Abdel Halim Harrath
- Zoology Department, College of Science, King Saud University, Riyadh 11451, Saudi Arabia;
| | - Seungjoon Moon
- Department of Pathology, College of Korean Medicine, Kyung Hee University, 1–5 Hoegidong Dongdaemun-gu, Seoul 02447, Republic of Korea;
| | - Bonglee Kim
- Department of Pathology, College of Korean Medicine, Kyung Hee University, 1–5 Hoegidong Dongdaemun-gu, Seoul 02447, Republic of Korea;
- Korean Medicine-Based Drug Repositioning Cancer Research Center, College of Korean Medicine, Kyung Hee University, Seoul 02447, Republic of Korea
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12
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Kumar A, BharathwajChetty B, Manickasamy MK, Unnikrishnan J, Alqahtani MS, Abbas M, Almubarak HA, Sethi G, Kunnumakkara AB. Natural compounds targeting YAP/TAZ axis in cancer: Current state of art and challenges. Pharmacol Res 2024; 203:107167. [PMID: 38599470 DOI: 10.1016/j.phrs.2024.107167] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 04/01/2024] [Accepted: 04/02/2024] [Indexed: 04/12/2024]
Abstract
Cancer has become a burgeoning global healthcare concern marked by its exponential growth and significant economic ramifications. Though advancements in the treatment modalities have increased the overall survival and quality of life, there are no definite treatments for the advanced stages of this malady. Hence, understanding the diseases etiologies and the underlying molecular complexities, will usher in the development of innovative therapeutics. Recently, YAP/TAZ transcriptional regulation has been of immense interest due to their role in development, tissue homeostasis and oncogenic transformations. YAP/TAZ axis functions as coactivators within the Hippo signaling cascade, exerting pivotal influence on processes such as proliferation, regeneration, development, and tissue renewal. In cancer, YAP is overexpressed in multiple tumor types and is associated with cancer stem cell attributes, chemoresistance, and metastasis. Activation of YAP/TAZ mirrors the cellular "social" behavior, encompassing factors such as cell adhesion and the mechanical signals transmitted to the cell from tissue structure and the surrounding extracellular matrix. Therefore, it presents a significant vulnerability in the clogs of tumors that could provide a wide window of therapeutic effectiveness. Natural compounds have been utilized extensively as successful interventions in the management of diverse chronic illnesses, including cancer. Owing to their capacity to influence multiple genes and pathways, natural compounds exhibit significant potential either as adjuvant therapy or in combination with conventional treatment options. In this review, we delineate the signaling nexus of YAP/TAZ axis, and present natural compounds as an alternate strategy to target cancer.
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Affiliation(s)
- Aviral Kumar
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India
| | - Bandari BharathwajChetty
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India
| | - Mukesh Kumar Manickasamy
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India
| | - Jyothsna Unnikrishnan
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India
| | - Mohammed S Alqahtani
- Radiological Sciences Department, College of Applied Medical Sciences, King Khalid University, Abha 61421, Saudi Arabia; BioImaging Unit, Space Research Centre, Michael Atiyah Building, University of Leicester, Leicester LE1 7RH, United Kingdom
| | - Mohamed Abbas
- Electrical Engineering Department, College of Engineering, King Khalid University, Abha 61421, Saudi Arabia
| | - Hassan Ali Almubarak
- Division of Radiology, Department of Medicine, College of Medicine and Surgery, King Khalid University, Abha 61421, Saudi Arabia
| | - Gautam Sethi
- Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, 16 Medical Drive, Singapore 117600, Singapore; NUS Center for Cancer Research, Yong Loo Lin School of Medicine, National University of Singapore, 117699, Singapore.
| | - Ajaikumar B Kunnumakkara
- Cancer Biology Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati (IITG), Guwahati, Assam 781039, India.
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13
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Singh H, Chopra H, Singh I, Mohanto S, Ahmed MG, Ghumra S, Seelan A, Survase M, Kumar A, Mishra A, Mishra AK, Kamal MA. Molecular targeted therapies for cutaneous squamous cell carcinoma: recent developments and clinical implications. EXCLI JOURNAL 2024; 23:300-334. [PMID: 38655092 PMCID: PMC11036065 DOI: 10.17179/excli2023-6489] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Figures] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 02/14/2024] [Indexed: 04/26/2024]
Abstract
Cutaneous Squamous Cell Carcinoma (cSCC) is a common and potentially fatal type of skin cancer that poses a significant threat to public health and has a high prevalence rate. Exposure to ultraviolet radiation on the skin surface increases the risk of cSCC, especially in those with genetic syndromes like xerodermapigmentosum and epidermolysis bullosa. Therefore, understanding the molecular pathogenesis of cSCC is critical for developing personalized treatment approaches that are effective in cSCC. This article provides a comprehensive overview of current knowledge of cSCC pathogenesis, emphasizing dysregulated signaling pathways and the significance of molecular profiling. Several limitations and challenges associated with conventional therapies, however, are identified, stressing the need for novel therapeutic strategies. The article further discusses molecular targets and therapeutic approaches, i.e., epidermal growth factor receptor inhibitors, hedgehog pathway inhibitors, and PI3K/AKT/mTOR pathway inhibitors, as well as emerging molecular targets and therapeutic agents. The manuscript explores resistance mechanisms to molecularly targeted therapies and proposes methods to overcome them, including combination strategies, rational design, and optimization. The clinical implications and patient outcomes of molecular-targeted treatments are assessed, including response rates and survival outcomes. The management of adverse events and toxicities in molecular-targeted therapies is crucial and requires careful monitoring and control. The paper further discusses future directions for therapeutic advancement and research in this area, as well as the difficulties and constraints associated with conventional therapies.
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Affiliation(s)
- Harpreet Singh
- School of Pharmaceutical Sciences, IFTM University, Moradabad, U.P., India, 244102
| | - Hitesh Chopra
- Department of Biosciences, Saveetha School of Engineering, Saveetha Institute of Medical and Technical Sciences, Chennai - 602105, Tamil Nadu, India
| | - Inderbir Singh
- Chitkara College of Pharmacy, Chitkara University, Punjab, India
| | - Sourav Mohanto
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Center, Yenepoya (Deemed to be University), Mangalore, Karnataka, 575018, India
| | - Mohammed Gulzar Ahmed
- Department of Pharmaceutics, Yenepoya Pharmacy College & Research Center, Yenepoya (Deemed to be University), Mangalore, Karnataka, 575018, India
| | - Shruti Ghumra
- Department of Biological Sciences, Sunandan Divatia School of Science, NarseeMonjee Institute of Management Studies (NMIMS), Pherozeshah Mehta Rd, Mumbai, India, 400056
| | - Anmol Seelan
- Mahatma Gandhi Mission, Institute of Biosciences and Technology, Aurangabad, India
| | - Manisha Survase
- Mahatma Gandhi Mission, Institute of Biosciences and Technology, Aurangabad, India
| | - Arvind Kumar
- School of Pharmaceutical Sciences, IFTM University, Moradabad, U.P., India, 244102
| | - Amrita Mishra
- School of Pharmaceutical Sciences, Delhi Pharmaceutical Sciences and Research University, New Delhi, India, 110017
| | - Arun Kumar Mishra
- SOS School of Pharmacy, IFTM University, Moradabad, U.P., India, 244102
| | - Mohammad Amjad Kamal
- Institutes for Systems Genetics, Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, China
- King Fahd Medical Research Center, King Abdulaziz University, Saudi Arabia
- Department of Pharmacy, Faculty of Allied Health Sciences, Daffodil International University, Bangladesh
- Enzymoics, 7 Peterlee Place, Hebersham, NSW 2770; Novel Global Community Educational Foundation, Australia
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14
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Wang X, Yuan Z, Li Z, He X, Zhang Y, Wang X, Su J, Wu X, Li M, Du F, Chen Y, Deng S, Zhao Y, Shen J, Yi T, Xiao Z. Key oncogenic signaling pathways affecting tumor-infiltrating lymphocytes infiltration in hepatocellular carcinoma: basic principles and recent advances. Front Immunol 2024; 15:1354313. [PMID: 38426090 PMCID: PMC10902128 DOI: 10.3389/fimmu.2024.1354313] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2023] [Accepted: 01/29/2024] [Indexed: 03/02/2024] Open
Abstract
The incidence of hepatocellular carcinoma (HCC) ranks first among primary liver cancers, and its mortality rate exhibits a consistent annual increase. The treatment of HCC has witnessed a significant surge in recent years, with the emergence of targeted immune therapy as an adjunct to early surgical resection. Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has shown promising results in other types of solid tumors. This article aims to provide a comprehensive overview of the intricate interactions between different types of TILs and their impact on HCC, elucidate strategies for targeting neoantigens through TILs, and address the challenges encountered in TIL therapies along with potential solutions. Furthermore, this article specifically examines the impact of oncogenic signaling pathways activation within the HCC tumor microenvironment on the infiltration dynamics of TILs. Additionally, a concise overview is provided regarding TIL preparation techniques and an update on clinical trials investigating TIL-based immunotherapy in solid tumors.
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Affiliation(s)
- Xiang Wang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Zijun Yuan
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Zhengbo Li
- Department of Laboratory Medicine, The Longmatan District People’s Hospital, Luzhou, China
| | - Xinyu He
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Yinping Zhang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xingyue Wang
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Jiahong Su
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
| | - Xu Wu
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Mingxing Li
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Fukuan Du
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Yu Chen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Shuai Deng
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Yueshui Zhao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Jing Shen
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
| | - Tao Yi
- School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, Hong Kong SAR, China
| | - Zhangang Xiao
- Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, China
- Cell Therapy and Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China
- South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China
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15
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Hong S, Zhang J, Liu S, Jin Q, Li J, Xia A, Xu J. Protein profiles reveal MSH6/MSH2 as a potential biomarker for hepatocellular carcinoma with microvascular invasion. Hepatol Res 2024; 54:189-200. [PMID: 37776019 DOI: 10.1111/hepr.13971] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/19/2023] [Revised: 09/23/2023] [Accepted: 09/26/2023] [Indexed: 10/01/2023]
Abstract
AIM Microvascular invasion (MVI) is an independent risk factor for postoperative recurrence and metastasis in hepatocellular carcinoma (HCC). However, the specific protein expression profiles that differentiate HCC with MVI from those without MVI remain unclear. METHODS The profiles of proteins in early-stage HCC tissues and normal liver tissues were characterized by quantitative proteomics techniques. Immunohistochemical (IHC) staining was undertaken on tissue microarrays from 80 HCC patients to assess the expression of MSH2 and MSH6. Cell counting, colony formation, migration, and invasion assays were carried out in vitro. RESULTS We identified 5164 proteins in both HCC tissues and adjacent normal liver tissues. Compared to HCC without MVI, 148 upregulated proteins and 97 downregulated proteins were found in HCC with MVI. Particularly noteworthy was the remarkable upregulation of MSH6/MSH2 among these dysregulated proteins in HCC with MVI. Further validation through bioinformatics prediction and IHC confirmed the elevated expression of MSH6/MSH2, which correlated with aggressive disease characteristics and poor prognosis. Receiver operating characteristic curve analyses revealed a substantial area under the curve of 0.761 (specificity 71.79%, sensitivity 73.17%) for the combined use of MSH6/MSH2. Knockdown of MSH6/MSH2 significantly inhibited HCC cell proliferation and invasion in vitro. CONCLUSIONS Our study establishes MSH6 or MSH2 as an oncogene that is prominently overexpressed during HCC progression, which provides new targets for HCC with MVI.
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Affiliation(s)
- Shengqian Hong
- Department of Hepatobiliary Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Jialing Zhang
- Department of Hepatobiliary Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Shiqi Liu
- Department of Hepatobiliary Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Quan Jin
- Department of Hepatobiliary Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Jingqi Li
- Department of Pathology, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
| | - Anliang Xia
- Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China
| | - JianBo Xu
- Department of Hepatobiliary Surgery, The Affiliated Huaian No. 1 People's Hospital of Nanjing Medical University, Huai'an, China
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16
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Ji G, Li Y, Zhang Z, Li H, Sun P. Recent advances of novel targeted drug delivery systems based on natural medicine monomers against hepatocellular carcinoma. Heliyon 2024; 10:e24667. [PMID: 38312669 PMCID: PMC10834828 DOI: 10.1016/j.heliyon.2024.e24667] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2023] [Revised: 12/22/2023] [Accepted: 01/11/2024] [Indexed: 02/06/2024] Open
Abstract
Hepatocellular carcinoma (HCC), the most prevalent type of liver cancer, is often diagnosed at an advanced stage. Surgical interventions are often ineffective, leading HCC patients to rely on systemic chemotherapy. Unfortunately, commonly used chemotherapeutic drugs have limited efficacy and can adversely affect vital organs, causing significant physical and psychological distress for patients. Natural medicine monomers (NMMs) have shown promising efficacy and safety profiles in HCC treatment, garnering attention from researchers. In recent years, the development of novel targeted drug delivery systems (TDDS) combining NMMs with nanocarriers has emerged. These TDDS aim to concentrate drugs effectively in HCC cells by manipulating the characteristics of nanomedicines, leveraging receptor and ligand interactions, and utilizing endogenous stimulatory responses to promote specific nanomedicines distribution. This comprehensive review presents recent research on TDDS for HCC treatment using NMMs from three perspectives: passive TDDS, active TDDS, and stimuli-responsive drug delivery systems (SDDS). It consolidates the current state of research on TDDS for HCC treatment with NMMs and highlights the potential of these innovative approaches in improving treatment outcomes. Moreover, the review also identifies research gaps in the related fields to provide references for future targeted therapy research in HCC.
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Affiliation(s)
- Guanjie Ji
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
| | - Yue Li
- Department of Clinical Pharmacy, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
| | - Zhiyue Zhang
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province, 250012, China
| | - Hui Li
- Department of Pharmaceutics, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong Province, 250012, China
| | - Ping Sun
- School of Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China
- Grade Three Laboratory of Traditional Chinese Medicine Preparation of the National Administration of Traditional Chinese Medicine, Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, 250014, China
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17
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Naderi N, Mohammadgholi A, Asghari Moghaddam N. Biosynthesis of Copper Oxide-Silver Nanoparticles from Ephedra Intermedia Extract and Study of Anticancer Effects in HepG2 Cell Line: Apoptosis-Related Genes Analysis and Nitric Oxide Level Investigations. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE 2024; 13:303-324. [PMID: 39493510 PMCID: PMC11530949 DOI: 10.22088/ijmcm.bums.13.3.303] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2024] [Accepted: 08/26/2024] [Indexed: 11/05/2024]
Abstract
Liver cancer treatment faces significant obstacles such as resistance, recurrence, metastasis, and toxicity to healthy cells. Biometallic nanoparticles (NPs) have emerged as a promising approach to address these challenges. In this study, copper oxide-silver (Ag-doped CuO) NPs were prepared using a reduction method with Ephedra intermedia extract. The physicochemical properties of the NPs were evaluated using various techniques such as Field emission scanning electron microscopy (FESEM), Transmission Electron Microscope (TEM), X-ray diffraction (XRD), and Fourier-transform infrared spectroscopy (FTIR). Additionally, this study has evaluated nitric oxide levels (NO), reactive oxygen species (ROS) production, Bax, Bcl2, P53, and Caspase3 genes expression, as well as cell viability within 24 hours in liver cancer cell line HepG2. FESEM and TEM imaging confirmed the nanostructural nature of the synthesized particles with sizes ranging from 31.27 to 88.98 nanometers. XRD analysis confirmed the crystal structure of the NPs. Comparative analysis showed that the IC50 values of the Ag-doped CuO NPs were significantly lower than that of the plant extracts. Molecular studies showed significantly increased expression of Bax, Caspase3, and P53 genes, inducing apoptosis in cancer cells, and downregulation of Bcl2 as a pro-metastasis gene. Additionally, the presence of Ag-doped CuO NPs significantly increased NO activity enzyme and ROS generation compared to the plant extract. The biosynthesized Ag-doped CuO NPs demonstrated the ability to induce apoptosis, increase ROS production, and enhance NO enzyme activity in HepG2 cancer cells, suggesting their potential as a therapeutic agent for liver cancer.
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Affiliation(s)
| | - Azadeh Mohammadgholi
- Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran.
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18
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Hu Q, Zhang W, Wei F, Huang M, Shu M, Song D, Wen J, Wang J, Nian Q, Ma X, Zeng J, Zhao Y. Human diet-derived polyphenolic compounds and hepatic diseases: From therapeutic mechanisms to clinical utilization. Phytother Res 2024; 38:280-304. [PMID: 37871899 DOI: 10.1002/ptr.8043] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2023] [Revised: 09/12/2023] [Accepted: 10/01/2023] [Indexed: 10/25/2023]
Abstract
This review focuses on the potential ameliorative effects of polyphenolic compounds derived from human diet on hepatic diseases. It discusses the molecular mechanisms and recent advancements in clinical applications. Edible polyphenols have been found to play a therapeutic role, particularly in liver injury, liver fibrosis, NAFLD/NASH, and HCC. In the regulation of liver injury, polyphenols exhibit anti-inflammatory and antioxidant effects, primarily targeting the TGF-β, NF-κB/TLR4, PI3K/AKT, and Nrf2/HO-1 signaling pathways. In the regulation of liver fibrosis, polyphenolic compounds effectively reverse the fibrotic process by inhibiting the activation of hepatic stellate cells (HSC). Furthermore, polyphenolic compounds show efficacy against NAFLD/NASH by inhibiting lipid oxidation and accumulation, mediated through the AMPK, SIRT, and PPARγ pathways. Moreover, several polyphenolic compounds exhibit anti-HCC activity by suppressing tumor cell proliferation and metastasis. This inhibition primarily involves blocking Akt and Wnt signaling, as well as inhibiting the epithelial-mesenchymal transition (EMT). Additionally, clinical trials and nutritional evidence support the notion that certain polyphenols can improve liver disease and associated metabolic disorders. However, further fundamental research and clinical trials are warranted to validate the efficacy of dietary polyphenols.
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Affiliation(s)
- Qichao Hu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
| | - Wenwen Zhang
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Feng Wei
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Meilan Huang
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Mengyao Shu
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Dan Song
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jianxia Wen
- School of Food and Bioengineering, Xihua University, Chengdu, China
| | - Jundong Wang
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Qing Nian
- Department of Blood Transfusion, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Xiao Ma
- State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Jinhao Zeng
- School of Clinical Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China
- TCM Regulating Metabolic Diseases Key Laboratory of Sichuan Province, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
- Department of Gastroenterology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China
| | - Yanling Zhao
- Department of Pharmacy, Chinese PLA General Hospital, Beijing, China
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Zaafar D, Khalil HMA, Elnaggar R, Saad DZ, Rasheed RA. Protective role of hesperetin in sorafenib-induced hepato- and neurotoxicity in mice via modulating apoptotic pathways and mitochondrial reprogramming. Life Sci 2024; 336:122295. [PMID: 38007145 DOI: 10.1016/j.lfs.2023.122295] [Citation(s) in RCA: 4] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 11/20/2023] [Accepted: 11/22/2023] [Indexed: 11/27/2023]
Abstract
INTRODUCTION Sorafenib, an FDA-approved standard chemotherapy for advanced hepatocellular carcinoma, is associated with numerous adverse effects that significantly impact patients' physiological well-being. Consequently, identifying agents that mitigate these side effects while enhancing efficacy is crucial. Hesperetin, a flavone present in fruits and vegetables, possesses antioxidant, anti-inflammatory, and anti-cancer properties. This study aimed to investigate the hepatotoxic and neurotoxic effects of sorafenib and the potential protective role of hesperetin. MATERIALS AND METHODS Swiss albino mice were orally administered sorafenib (100 mg/kg) alone or in combination with hesperetin (50 mg/kg) over 21 days. Behavioral assessments for anxiety and depressive-like behaviors were conducted. Additionally, evaluations encompassed apoptotic activity, mitochondrial integrity, liver enzyme levels, proliferation rates, and histopathological changes. RESULTS Combining hesperetin with sorafenib showed improvements in behavioral alterations, liver damage, brain mitochondrial dysfunction, and liver apoptosis compared to the sorafenib-only group in mice. CONCLUSION Hesperetin exhibits potential as an adjunct to sorafenib, mitigating its side effects by attenuating its toxicity, enhancing efficacy, and potentially reducing the occurrence of sorafenib-induced resistance through the downregulation of hepatocyte growth factor levels.
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Affiliation(s)
- Dalia Zaafar
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Modern University, Cairo, Egypt.
| | - Heba M A Khalil
- Department of Veterinary Hygiene and Management, Faculty of Veterinary Medicine, Cairo University, Giza 12211, Egypt.
| | - Reham Elnaggar
- Department of Pharmacology and Toxicology, College of Pharmacy and Drug Manufacturing, Misr University of Science and Technology (MUST), 6th October, Giza 12566, Egypt.
| | - Diana Z Saad
- Department of Pathology, Faculty of Medicine, Ain Shams University, Cairo, Egypt; Department of Basic Medical Sciences, Faculty of Medicine, King Salman International University, South Sinai, Egypt.
| | - Rabab Ahmed Rasheed
- Department of Medical Histology and Cell Biology, Faculty of Medicine, King Salman International University, South Sinai, Egypt.
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ZHANG LINGLI, LI YAN, MAO JINGXIN. Research progress on natural products against hepatocellular carcinoma. BIOCELL 2024; 48:905-922. [DOI: 10.32604/biocell.2024.050396] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 04/24/2024] [Indexed: 11/26/2024]
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Mdlovu NV, Juang RS, Weng MT, Lin KS. Green synthesis and characterization of silicate nanostructures coated with Pluronic F127/gelatin for triggered drug delivery in tumor microenvironments. Int J Biol Macromol 2023; 251:126337. [PMID: 37586620 DOI: 10.1016/j.ijbiomac.2023.126337] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2023] [Revised: 08/11/2023] [Accepted: 08/12/2023] [Indexed: 08/18/2023]
Abstract
Thermo-/pH-sensitive nanocomposites based on mesoporous silicate MCM-41 (MSNCs) derived from rice husk ash were synthesized and characterized. MSNCs were coated with thermo-/pH-sensitive Pluronic® F127 and gelatin to form MSNCs@gp nanocomposites, serving as carriers for controlled release of the anticancer drug doxorubicin (Dox). The in vitro and in vivo antitumor efficacy of MSNCs@gp-Dox against liver cancer was evaluated. Fourier-transform infrared (FTIR) spectra confirmed the silica nature of MSNCs@gp by detecting the Si-O-Si group. Under acidic microenvironments (pH 5.4) and 42 °C, MSNCs@gp-Dox exhibited significantly higher Dox release (47.33 %) compared to physiological conditions. Thermo-/pH-sensitive drug release (47.33 %) was observed in simulated tumor environments. The Makoid-Banakar model provided the best fit at pH 7.4 and 37 °C with a mean squared error of 0.4352, an Akaike Information Criterion of 15.00, and a regression coefficient of 0.9972. Cytotoxicity tests have demonstrated no significant toxicity in HepG2 cells treated with various concentrations of MSNCs@gp, while MSNCs@gp-Dox induced considerable cell apoptosis. In vivo studies in nude mice revealed effective suppression of liver cancer growth by MSNCs@gp-Dox, indicating high pharmaceutical efficacy. The investigated MSNCs@gp-based drug delivery system shows promise for liver cancer therapy, offering enhanced treatment efficiency with minimal side effects.
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Affiliation(s)
- Ndumiso Vukile Mdlovu
- Department of Chemical and Materials Engineering, Chang Gung University, Guishan, Taoyuan 33302, Taiwan; Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital Linkou, Taoyuan 33305, Taiwan; Department of Chemical Engineering and Materials Science, Yuan Ze University, Chungli, Taoyuan 32003, Taiwan
| | - Ruey-Shin Juang
- Department of Chemical and Materials Engineering, Chang Gung University, Guishan, Taoyuan 33302, Taiwan; Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital Linkou, Taoyuan 33305, Taiwan; Department of Safety, Health and Environmental Engineering, Ming Chi University of Technology, Taishan, New Taipei City 24301, Taiwan.
| | - Meng-Tzu Weng
- Department of Internal Medicine, National Taiwan University Hospital, Taipei 100233, Taiwan; Department of Medical Research, National Taiwan University Hospital Hsinchu Branch, Hsinchu 302, Taiwan.
| | - Kuen-Song Lin
- Department of Chemical Engineering and Materials Science, Yuan Ze University, Chungli, Taoyuan 32003, Taiwan.
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Kumar S, Senapati S, Bhattacharya N, Bhattacharya A, Maurya SK, Husain H, Bhatti JS, Pandey AK. Mechanism and recent updates on insulin-related disorders. World J Clin Cases 2023; 11:5840-5856. [PMID: 37727490 PMCID: PMC10506040 DOI: 10.12998/wjcc.v11.i25.5840] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2023] [Revised: 07/06/2023] [Accepted: 08/07/2023] [Indexed: 09/01/2023] Open
Abstract
Insulin, a small protein with 51 amino acids synthesized by pancreatic β-cells, is crucial to sustain glucose homeostasis at biochemical and molecular levels. Numerous metabolic dysfunctions are related to insulin-mediated altered glucose homeostasis. One of the significant pathophysiological conditions linked to the insulin associated disorder is diabetes mellitus (DM) (type 1, type 2, and gestational). Insulin resistance (IR) is one of the major underlying causes of metabolic disorders despite its association with several physiological conditions. Metabolic syndrome (MS) is another pathophysiological condition that is associated with IR, hypertension, and obesity. Further, several other pathophysiological disorders/diseases are associated with the insulin malfunctioning, which include polycystic ovary syndrome, neuronal disorders, and cancer. Insulinomas are an uncommon type of pancreatic β-cell-derived neuroendocrine tumor that makes up 2% of all pancreatic neoplasms. Literature revealed that different biochemical events, molecular signaling pathways, microRNAs, and microbiota act as connecting links between insulin disorder and associated pathophysiology such as DM, insuloma, neurological disorder, MS, and cancer. In this review, we focus on the insulin-related disorders and the underlying mechanisms associated with the pathophysiology.
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Affiliation(s)
- Shashank Kumar
- Department of Biochemistry, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Sabyasachi Senapati
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Neetu Bhattacharya
- Department of Zoology, Dyal Singh College, University of Delhi, New Delhi 110003, India
| | - Amit Bhattacharya
- Department of Zoology, Ramjas College, University of Delhi, New Delhi 110007, India
| | | | - Hadiya Husain
- Department of Zoology, University of Lucknow, Lucknow 226007, India
| | - Jasvinder Singh Bhatti
- Department of Human Genetics and Molecular Medicine, Central University of Punjab, Bathinda 151401, Punjab, India
| | - Abhay Kumar Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj) 211002, India
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Kumar R, Kushwaha PP, Singh AK, Kumar S, Pandey AK. Anti-proliferative, apoptosis inducing, and antioxidant potential of Callistemon lanceolatus bark extracts: an in vitro and in silico study. Med Oncol 2023; 40:169. [PMID: 37156972 DOI: 10.1007/s12032-023-02035-4] [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: 03/18/2023] [Accepted: 04/19/2023] [Indexed: 05/10/2023]
Abstract
The present study reports anticancer and antioxidant activities of Callistemon lanceolatus bark extracts. Anticancer activity was studied against MDA-MB-231 cells. Antioxidant assessment of the chloroform and methanol extracts showed considerable free radical scavenging, metal ion chelating, and reducing power potential. Chloroform extract exhibited potent inhibition of cancer cell proliferation in MTT assay (IC50 9.6 μg/ml) and promoted programmed cell death. Reactive oxygen species (ROS) generation, mitochondria membrane potential (MMP) disruption ability, and nuclear morphology changes were studied using H2-DCFDA, JC-1, and Hoechst dyes, respectively, using confocal microscopy. Apoptotic cells exhibited fragmented nuclei, increased ROS generation, and altered MMP in dose- and time-dependent manner. Chloroform extract upregulated the BAX-1 and CASP3 mRNA expression coupled with downregulation of BCL-2 gene. Further, in silico docking of phytochemicals present in C. lanceolatus with anti-apoptotic Bcl-2 protein endorsed apoptosis by its inhibition and thus corroborated the experimental findings. Obatoclax, a known inhibitor of Bcl-2 was used as a reference compounds.
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Affiliation(s)
- Ramesh Kumar
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj), 211002, Uttar Pradesh, India
- Department of Biochemistry, Central University of Punjab, Bathinda, 151401, Punjab, India
| | - Prem Prakash Kushwaha
- Department of Biochemistry, Central University of Punjab, Bathinda, 151401, Punjab, India
| | - Atul Kumar Singh
- Department of Biochemistry, Central University of Punjab, Bathinda, 151401, Punjab, India
| | - Shashank Kumar
- Department of Biochemistry, Central University of Punjab, Bathinda, 151401, Punjab, India
| | - Abhay Kumar Pandey
- Department of Biochemistry, University of Allahabad, Allahabad (Prayagraj), 211002, Uttar Pradesh, India.
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