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Wan X, Wang D. Curcumin: Epigenetic Modulation and Tumor Immunity in Antitumor Therapy. PLANTA MEDICA 2025. [PMID: 39689889 DOI: 10.1055/a-2499-1140] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/19/2024]
Abstract
Curcumin (turmeric) is the main ingredient of the Chinese herbal turmeric rhizome, used to treat tumors, diabetes, inflammation, neurodegenerative diseases, cardiovascular diseases, metabolic syndrome, and liver diseases. The antitumor effects of curcumin have received even more attention. One of the main mechanisms of the antitumor effects includes inhibition of tumor invasion and migration, induction of tumor cell apoptosis, and inhibition of various cell signaling pathways. It has been found that the antitumor biological activity of curcumin in the body is associated with epigenetic mechanisms. That also implies that curcumin may act as a potential epigenetic modulator to influence the development of tumor diseases. The immune system plays an essential role in the development of tumorigenesis. Tumor immunotherapy is currently one of the most promising research directions in the field of tumor therapy. Curcumin has been found to have significant regulatory effects on tumor immunity and is expected to be a novel adjuvant for tumor immunity. This paper summarizes the antitumor effects of curcumin from four aspects: molecular and epigenetic mechanisms of curcumin against a tumor, mechanisms of curcumin modulation of tumor immunotherapy, reversal of chemotherapy resistance, and a novel drug delivery system of curcumin, which provide new directions for the development of new antitumor drugs.
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Affiliation(s)
- Xin Wan
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
| | - Dong Wang
- Tianjin University of Traditional Chinese Medicine, Tianjin, China
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2
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Karatayli E, Sadiq SC, Schattenberg JM, Grabbe S, Biersack B, Kaps L. Curcumin and Its Derivatives in Hepatology: Therapeutic Potential and Advances in Nanoparticle Formulations. Cancers (Basel) 2025; 17:484. [PMID: 39941855 PMCID: PMC11816286 DOI: 10.3390/cancers17030484] [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: 12/20/2024] [Revised: 01/19/2025] [Accepted: 01/21/2025] [Indexed: 02/16/2025] Open
Abstract
Curcumin, a plant-derived polyphenol, shows promise in hepatology for treating both malignant and non-malignant liver diseases and a subset of extrahepatic cancers. Curcumin has hepatoprotective, anti-inflammatory, antifibrotic, and antiproliferative properties, as is evident in preclinical and clinical studies. This highlights its potential as an adjunct to established cancer therapies, especially in the context of hepatocellular carcinoma and secondary liver malignancies. Curcumin also demonstrates potential in metabolic dysfunction-associated steatotic liver disease (MASLD), owing to its antifibrotic and lipid-lowering effects. However, its clinical use is limited, relating to its poor bioavailability and rapid metabolism. Nanotechnology, including liposomal and polymeric carriers, alongside synthetic curcumin derivatives, offers strategies to enhance the bioavailability and pharmacokinetic properties. We propose to revisit the use of curcumin in nanoparticle preparations in chronic liver disease and summarize current evidence in this review article.
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Affiliation(s)
- Ersin Karatayli
- Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany; (E.K.); (S.C.S.); (J.M.S.)
| | - Shifana C. Sadiq
- Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany; (E.K.); (S.C.S.); (J.M.S.)
| | - Jörn M. Schattenberg
- Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany; (E.K.); (S.C.S.); (J.M.S.)
| | - Stephan Grabbe
- Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, 55128 Mainz, Germany;
| | - Bernhard Biersack
- Organic Chemistry Laboratory, University of Bayreuth, 95440 Bayreuth, Germany
| | - Leonard Kaps
- Department of Medicine II, Saarland University Medical Center, Saarland University, 66421 Homburg, Germany; (E.K.); (S.C.S.); (J.M.S.)
- Department of Dermatology, University Medical Center of the Johannes Gutenberg-University, 55128 Mainz, Germany;
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Wan H, Zhang YX, Shan GY, Cheng JY, Qiao DR, Liu YY, Shi WN, Li HJ. Antiviral therapy for hepatitis B virus infection is beneficial for the prognosis hepatocellular carcinoma. World J Gastrointest Oncol 2025; 17:93983. [PMID: 39817121 PMCID: PMC11664622 DOI: 10.4251/wjgo.v17.i1.93983] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2024] [Revised: 09/20/2024] [Accepted: 09/29/2024] [Indexed: 12/12/2024] Open
Abstract
In this editorial, we comment on the article by Mu et al, published in the recent issue of the World Journal of Gastrointestinal Oncology. We pay special attention to the immune tolerance mechanism caused by hepatitis B virus (HBV) infection, the pathogenesis of hepatocellular carcinoma (HCC), and the role of antiviral therapy in treating HCC related to HBV infection. HBV infection leads to systemic innate immune tolerance by directly inhibiting pattern recognition receptor recognition and antiviral signaling pathways, as well as by inhibiting the immune functions of macrophages, natural killer cells and dendritic cells. In addition, HBV leads to an immunosuppressive cascade by expressing inhibitory molecules to induce exhaustion of HBV-specific cluster of differentiation 8 + T cells, ultimately leading to long-term viral infection. The loss of immune cell function caused by HBV infection ultimately leads to HCC. Long-term antiviral therapy can improve the prognosis of patients with HCC and prevent tumor recurrence and metastasis.
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Affiliation(s)
- Hui Wan
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Yu-Xin Zhang
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Guan-Yue Shan
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
| | - Jun-Ya Cheng
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
- Department of Bioengineering, Pharmacy School of Jilin University, Changchun 130061, Jilin Province, China
| | - Duan-Rui Qiao
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
- Department of Bioengineering, Pharmacy School of Jilin University, Changchun 130061, Jilin Province, China
| | - Yi-Ying Liu
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
- Department of Bioengineering, Pharmacy School of Jilin University, Changchun 130061, Jilin Province, China
| | - Wen-Na Shi
- Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
- Department of Bioengineering, Pharmacy School of Jilin University, Changchun 130061, Jilin Province, China
| | - Hai-Jun Li
- Institute of Liver Diseases, Institute of Translational Medicine, The First Hospital of Jilin University, Changchun 130061, Jilin Province, China
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Deng LQ, Li SY, Xie T, Zeng WQ, Wang YY, Shi CJ, Jin-Fang Z. LincROR promotes tumor growth of colorectal cancer through the miR-145/WNT2B/WNT10A/Wnt/β-catenin regulatory axis. PLoS One 2024; 19:e0312417. [PMID: 39546475 PMCID: PMC11567539 DOI: 10.1371/journal.pone.0312417] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2024] [Accepted: 10/05/2024] [Indexed: 11/17/2024] Open
Abstract
Colorectal cancer (CRC) is a prevalent form of malignant tumor, and the current clinical treatments are far from satisfactory. Identifying new therapeutic targets is therefore essential for clinical practices. The long intergenic non-protein coding RNA lincROR has been shown to play a significant role in the tumorigenesis of various cancers. However, the molecular mechanism underlying lincROR-mediated CRC tumorigenesis remains unclear. In the present study, we found that knockdown of lincROR significantly inhibited cell viability in vitro, while its overexpression promoted tumor growth in vivo. Mechanistically, lincROR acted as a miRNA sponge for miR-145, thereby elevating the expression of the target genes WNT2B and WNT10A. The overexpression of WNT2B and WNT10A definitely activated the Wnt/β-catenin pathway, thus led to promoting tumorigenesis in CRC. In summary, our findings identified lincROR as a novel activator of the Wnt/β-catenin pathway by serving as a miRNA sponge for miR-145 and facilitating tumorigenesis, which suggests that lincROR may be a potential therapeutic target for CRC patients.
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Affiliation(s)
- Li-Qiang Deng
- Shenzhen Traditional Chinese Medicine Oncology Center, Shenzhen, Guangdong, P. R. China
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, P. R. China
| | - Shi-Ying Li
- Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China
| | - Tian Xie
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, P. R. China
| | - Wei-Qiang Zeng
- Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, P. R. China
| | - Yu-Yan Wang
- Shenzhen Traditional Chinese Medicine Oncology Center, Shenzhen, Guangdong, P. R. China
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, P. R. China
| | - Chuan-Jian Shi
- Shenzhen Traditional Chinese Medicine Oncology Center, Shenzhen, Guangdong, P. R. China
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, P. R. China
| | - Zhang Jin-Fang
- Shenzhen Traditional Chinese Medicine Oncology Center, Shenzhen, Guangdong, P. R. China
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, P. R. China
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Ma S, Meng G, Liu T, You J, He R, Zhao X, Cui Y. The Wnt signaling pathway in hepatocellular carcinoma: Regulatory mechanisms and therapeutic prospects. Biomed Pharmacother 2024; 180:117508. [PMID: 39362068 DOI: 10.1016/j.biopha.2024.117508] [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: 06/15/2024] [Revised: 08/26/2024] [Accepted: 09/25/2024] [Indexed: 10/05/2024] Open
Abstract
Hepatocellular carcinoma (HCC) is a malignant tumor that arises from hepatocytes. Multiple signaling pathways play a regulatory role in the occurrence and development of HCC, with the Wnt signaling pathway being one of the primary regulatory pathways. In normal hepatocytes, the Wnt signaling pathway maintains cell regeneration and organ development. However, when aberrant activated, the Wnt pathway is closely associated with invasion, cancer stem cells(CSCs), drug resistance, and immune evasion in HCC. Among these factors, the development of drug resistance is one of the most important factors affecting the efficacy of HCC treatment. These mechanisms form the basis for tumor cell adaptation and evolution within the body, enabling continuous changes in tumor cells, resistance to drugs and immune system attacks, leading to metastasis and recurrence. In recent years, there have been numerous new discoveries regarding these mechanisms. An increasing number of drugs targeting the Wnt signaling pathway have been developed, with some already entering clinical trials. Therefore, this review encompasses the latest research on the role of the Wnt signaling pathway in the onset and progression of HCC, as well as advancements in its therapeutic strategies.
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Affiliation(s)
- Shihui Ma
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Guorui Meng
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Tong Liu
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Junqi You
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Risheng He
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Xudong Zhao
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China
| | - Yunfu Cui
- Department of General Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150000, China.
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Gou Z, Zhang D, Cao H, Li Y, Li Y, Zhao Z, Wang Y, Wang Y, Zhou H. Exploring the nexus between MYH9 and tumors: novel insights and new therapeutic opportunities. Front Cell Dev Biol 2024; 12:1421763. [PMID: 39149512 PMCID: PMC11325155 DOI: 10.3389/fcell.2024.1421763] [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: 04/23/2024] [Accepted: 07/19/2024] [Indexed: 08/17/2024] Open
Abstract
The myosin heavy chain 9 (MYH9) gene, located on human chromosome 22, encodes non-muscle myosin heavy chain IIA (NM IIA). This protein is essential to various cellular events, such as generating intracellular chemomechanical force and facilitating the movement of the actin cytoskeleton. Mutations associated with thrombocytopenia in autosomal dominant diseases first highlighted the significance of the MYH9 gene. In recent years, numerous studies have demonstrated the pivotal roles of MYH9 in various cancers. However, its effects on cancer are intricate and not fully comprehended. Furthermore, the elevated expression of MYH9 in certain malignancies suggests its potential as a target for tumor therapy. Nonetheless, there is a paucity of literature summarizing MYH9's role in tumors and the therapeutic strategies centered on it, necessitating a systematic analysis. This paper comprehensively reviews and analyzes the pertinent literature in this domain, elucidating the fundamental structural characteristics, biological functions, and the nexus between MYH9 and tumors. The mechanisms through which MYH9 contributes to tumor development and its multifaceted roles in the tumorigenic process are also explored. Additionally, we discuss the relationship between MYH9-related diseases (MYH9-RD) and tumors and also summarize tumor therapeutic approaches targeting MYH9. The potential clinical applications of studying the MYH9 gene include improving early diagnosis, clinical staging, and prognosis of tumors. This paper is anticipated to provide novel insights for tumor therapy.
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Affiliation(s)
- Zixuan Gou
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Difei Zhang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Hongliang Cao
- Department of Urology II, The First Hospital of Jilin University, Changchun, China
| | - Yao Li
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Yunkuo Li
- Department of Urology II, The First Hospital of Jilin University, Changchun, China
| | - Zijian Zhao
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Ye Wang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Yishu Wang
- Key Laboratory of Pathobiology, Ministry of Education, Jilin University, Changchun, China
| | - Honglan Zhou
- Department of Urology II, The First Hospital of Jilin University, Changchun, China
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Ghosh PK, Rao MJ, Putta CL, Ray S, Rengan AK. Telomerase: a nexus between cancer nanotherapy and circadian rhythm. Biomater Sci 2024; 12:2259-2281. [PMID: 38596876 DOI: 10.1039/d4bm00024b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/11/2024]
Abstract
Cancer represents a complex disease category defined by the unregulated proliferation and dissemination of anomalous cells within the human body. According to the GLOBOCAN 2020 report, the year 2020 witnessed the diagnosis of approximately 19.3 million new cases of cancer and 10.0 million individuals succumbed to the disease. A typical cell eventually becomes cancerous because of a long-term buildup of genetic instability and replicative immortality. Telomerase is a crucial regulator of cancer progression as it induces replicative immortality. In cancer cells, telomerase inhibits apoptosis by elongating the length of the telomeric region, which usually protects the genome from shortening. Many nanoparticles are documented as being available for detecting the presence of telomerase, and many were used as delivery systems to transport drugs. Furthermore, telomere homeostasis is regulated by the circadian time-keeping machinery, leading to 24-hour rhythms in telomerase activity and TERT mRNA expression in mammals. This review provides a comprehensive discussion of various kinds of nanoparticles used in telomerase detection, inhibition, and multiple drug-related pathways, as well as enlightens an imperative association between circadian rhythm and telomerase activity from the perspective of nanoparticle-based anticancer therapeutics.
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Affiliation(s)
- Pramit Kumar Ghosh
- Department of Biomedical Engineering, Indian Institute of Technology (IIT), Hyderabad, India.
| | - Maddila Jagapathi Rao
- Department of Biomedical Engineering, Indian Institute of Technology (IIT), Hyderabad, India.
| | - Chandra Lekha Putta
- Department of Biomedical Engineering, Indian Institute of Technology (IIT), Hyderabad, India.
| | - Sandipan Ray
- Department of Biotechnology, Indian Institute of Technology (IIT), Hyderabad, India.
| | - Aravind Kumar Rengan
- Department of Biomedical Engineering, Indian Institute of Technology (IIT), Hyderabad, India.
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Alkan AH, Ensoy M, Cansaran-Duman D. Strategic and Innovative Roles of lncRNAs Regulated by Naturally-derived Small Molecules in Cancer Therapy. Curr Med Chem 2024; 31:6672-6691. [PMID: 37921177 DOI: 10.2174/0109298673264372230919102758] [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: 05/27/2023] [Revised: 07/22/2023] [Accepted: 08/17/2023] [Indexed: 11/04/2023]
Abstract
In the field of precision and personalized medicine, the next generation sequencing method has begun to take an active place as genome-wide screening applications in the diagnosis and treatment of diseases. Studies based on the determination of the therapeutic efficacy of personalized drug use in cancer treatment in the size of the transcriptome and its extension, lncRNA, have been increasing rapidly in recent years. Targeting and/or regulating noncoding RNAs (ncRNAs) consisting of long noncoding RNAs (lncRNAs) are promising strategies for cancer treatment. Within the scope of rapidly increasing studies in recent years, it has been shown that many natural agents obtained from biological organisms can potentially alter the expression of many lncRNAs associated with oncogenic functions. Natural agents include effective small molecules that provide anti-cancer effects and have been used as chemotherapy drugs or in combination with standard anti-cancer drugs used in routine treatment. In this review, it was aimed to provide detailed information about the potential of natural agents to regulate and/or target non-coding RNAs and their mechanisms of action to provide an approach for cancer therapy. The discovery of novel anti-cancer targets and subsequent development of effective drugs or combination strategies that are still needed for most cancers will be promising for cancer treatment.
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Affiliation(s)
- Ayşe Hale Alkan
- Biotechnology Institute, Ankara University, Keçiören, Ankara, Turkey
- Department of Molecular Biology and Genetics, Faculty of Science, Bartın University, Bartın, Turkey
| | - Mine Ensoy
- Biotechnology Institute, Ankara University, Keçiören, Ankara, Turkey
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Liu F, Meng L, Wang H, Du C, Zhu J, Xiong Q, Sun W. Research on preparation and antitumor activity of redox-responsive polymer micelles co-loaded with sorafenib and curcumin. JOURNAL OF BIOMATERIALS SCIENCE. POLYMER EDITION 2023; 34:2179-2197. [PMID: 37369107 DOI: 10.1080/09205063.2023.2230845] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/24/2023] [Revised: 05/21/2023] [Accepted: 05/25/2023] [Indexed: 06/29/2023]
Abstract
A novel redox-responsive mPEG-SS-PLA (PSP) polymeric micelle was synthesized and prepared for the delivery of sorafenib (SAF) and curcumin (CUR). And a series of validations were conducted to confirm the structure of the synthesized polymer carriers. Using the Chou-Talalay approach, the combination indexes (CI) of SAF and CUR were determined, and explore the inhibitory effects of the two drugs on HepG2R cells at different ratios. SAF/CUR-PSP polymeric micelles were prepared by thin film hydration method, and the physicochemical properties of nanomicelles were evaluated. The biocompatibility, cell uptake, cell migration, and cytotoxicity assays were assessed in HepG2R cells. The expression of the phosphoinositol-3 kinase (PI3K)/serine/threonine kinase (Akt) signaling pathway was detected by Western blot assay. Additionally, the tumor suppressive effect of SAF/CUR-PSP micelles was clearly superior to free drug monotherapy or their physical combination in HepG2 cell-induced tumor xenografts. The current study revealed that mPEG-SS-PLA polymer micelles loaded with SAF and CUR showed the enhanced therapeutic effects against hepatocellular carcinoma in vitro and in vivo models. It has promising applications for cancer therapy.
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Affiliation(s)
- Fangshu Liu
- College of Pharmacy, Jiamusi University, Jiamusi City, Heilongjiang Province, China
| | - Lei Meng
- College of Pharmacy, Jiamusi University, Jiamusi City, Heilongjiang Province, China
| | - Heran Wang
- College of Pharmacy, Jiamusi University, Jiamusi City, Heilongjiang Province, China
| | - Chenchen Du
- College of Pharmacy, Jiamusi University, Jiamusi City, Heilongjiang Province, China
| | - Jiaying Zhu
- College of Pharmacy, Jiamusi University, Jiamusi City, Heilongjiang Province, China
| | - Qian Xiong
- College of Pharmacy, Jiamusi University, Jiamusi City, Heilongjiang Province, China
| | - Weitong Sun
- College of Pharmacy, Jiamusi University, Jiamusi City, Heilongjiang Province, China
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El-Aziz MKA, Dawoud A, Kiriacos CJ, Fahmy SA, Hamdy NM, Youness RA. Decoding hepatocarcinogenesis from a noncoding RNAs perspective. J Cell Physiol 2023; 238:1982-2009. [PMID: 37450612 DOI: 10.1002/jcp.31076] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2023] [Revised: 06/11/2023] [Accepted: 06/19/2023] [Indexed: 07/18/2023]
Abstract
Being a leading lethal malignancy worldwide, the pathophysiology of hepatocellular carcinoma (HCC) has gained a lot of interest. Yet, underlying mechanistic basis of the liver tumorigenesis is poorly understood. The role of some coding genes and their respective translated proteins, then later on, some noncoding RNAs (ncRNAs) such as microRNAs have been extensively studied in context of HCC pathophysiology; however, the implication of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in HCC is indeed less investigated. As a subclass of the ncRNAs which has been elusive for long time ago, lncRNAs was found to be involved in plentiful cellular functions such as DNA, RNA, and proteins regulation. Hence, it is undisputed that lncRNAs dysregulation profoundly contributes to HCC via diverse etiologies. Accordingly, lncRNAs represent a hot research topic that requires prime focus in HCC. In this review, the authors discuss breakthrough discoveries involving lncRNAs and circRNAs dysregulation that have contributed to the contemporary concepts of HCC pathophysiology and how these concepts could be leveraged as potential novel diagnostic and prognostic HCC biomarkers. Further, this review article sheds light on future trends, thereby discussing the pathological roles of lncRNAs and circRNAs in HCC proliferation, migration, and epithelial-to-mesenchymal transition. Along this line of reasoning, future recommendations of how these targets could be exploited to achieve effective HCC-related drug development is highlighted.
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Affiliation(s)
- Mostafa K Abd El-Aziz
- Biochemistry Department, Faculty of Pharmacy, Al-Azhar University, Assiut Branch, Assiut, Egypt
- Molecular Genetics Research Team (MGRT), Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo, Egypt
| | - Alyaa Dawoud
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Caroline J Kiriacos
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
| | - Sherif Ashraf Fahmy
- Chemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo, Egypt
| | - Nadia M Hamdy
- Biochemistry Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt
| | - Rana A Youness
- Molecular Genetics Research Team (MGRT), Biology and Biochemistry Department, School of Life and Medical Sciences, University of Hertfordshire Hosted by Global Academic Foundation, Cairo, Egypt
- Molecular Genetics Research Team (MGRT), Pharmaceutical Biology Department, Faculty of Pharmacy and Biotechnology, German University in Cairo, Cairo, Egypt
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11
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The Role of Ferroptosis and Cuproptosis in Curcumin against Hepatocellular Carcinoma. Molecules 2023; 28:molecules28041623. [PMID: 36838613 PMCID: PMC9964324 DOI: 10.3390/molecules28041623] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2022] [Revised: 01/31/2023] [Accepted: 02/06/2023] [Indexed: 02/10/2023] Open
Abstract
BACKGROUND Among cancer-related deaths, hepatocellular carcinoma (HCC) ranks fourth, and traditional Chinese medicine (TCM) treatment is an important complementary alternative therapy for HCC. Curcumin is a natural ingredient extracted from Curcuma longa with anti-HCC activity, while the therapeutic mechanisms of curcumin remain unclear, especially on ferroptosis and cuproptosis. METHODS Differentially expressed genes (DEGs) of curcumin treatment in PLC, KMCH, and Huh7 cells were identified, respectively. The common genes among them were then obtained to perform functional enrichment analysis and prognostic analysis. Moreover, weighted gene co-expression network analysis (WGCNA) was carried out for the construction of the co-expression network. The ferroptosis potential index (FPI) and the cuproptosis potential index (CPI) were subsequently used to quantitatively analyze the levels of ferroptosis and cuproptosis. Finally, single-cell transcriptome analysis of liver cancer was conducted. RESULTS We first identified 702, 515, and 721 DEGs from curcumin-treated PLC, KMCH, and Huh7 cells, respectively. Among them, HMOX1, CYP1A1, HMGCS2, LCN2, and MTTP may play an essential role in metal ion homeostasis. By WGCNA, grey60 co-expression module was associated with curcumin treatment and involved in the regulation of ion homeostasis. Furthermore, FPI and CPI assessment showed that curcumin had cell-specific effects on ferroptosis and cuproptosis in different HCC cells. In addition, there are also significant differences in ferroptosis and cuproptosis levels among 16 HCC cell subtypes according to single-cell transcriptome data analysis. CONCLUSIONS We developed CPI and combined it with FPI to quantitatively analyze curcumin-treated HCC cells. It was found that ferroptosis and cuproptosis, two known metal ion-mediated forms of programmed cell death, may have a vital effect in treating HCC with curcumin, and there are significant differences in various liver cancer cell types and curcumin treatment which should be considered in the clinical application of curcumin.
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12
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Pang F, Ding S, Li N, Li Z, Tian N, Shi C, Zhang F, Mai Y, Zhang J, Wang J. Gallic acid mediates tumor-suppressive effects on osteosarcoma through the H19-Wnt/β-catenin regulatory axis. J Orthop Translat 2023; 39:34-42. [PMID: 36636358 PMCID: PMC9826808 DOI: 10.1016/j.jot.2022.12.003] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2022] [Revised: 12/06/2022] [Accepted: 12/07/2022] [Indexed: 01/06/2023] Open
Abstract
Background Osteosarcoma (OS) is the most common primary malignancy in bone tissues, and effective therapeutics remain absent in clinical practice. Traditional Chinese medicines (TCM) have been used for thousands of years, which provide great insights into OS management. Gallic acid (GA) is a natural phenolic acid enriched in various foods and herbs. Several pharmacological activities of GA such as anti-oxidation and anti-inflammation have been well-established. However, its biological function in OS remains not fully understood. Methods The potential anti-cancer properties of GA were evaluated in 143 B, U2OS and MG63 cells. Its effects on cell growth, cell cycle, apoptosis and migration were examined in these OS cells. The lncRNA H19 and Wnt/β-catenin signaling were detected by qPCR, luciferase activity and Western blotting assays. The in vivo effect of GA on tumor growth was investigated using an orthotopic mouse model. Results In the present study, GA was found to suppress the tumor growth in vitro via inducing cell cycle arrest and apoptosis in OS cells, and inhibit the invasion and metastasis as well. Using the orthotopic animal model, GA was also found to suppress tumorigenesis in vivo. Long noncoding RNA (lncRNA) H19 was demonstrated to be down-regulated by GA, and thus disrupted the canonical Wnt/β-catenin signaling in OS cells. Furthermore, the ectopic expression of H19 rescued the GA-induced suppressive effects on tumor growth and metastasis, and partially reversed the inactivation of Wnt/β-catenin signaling. Conclusions Taken together, our results indicated that GA inhibited tumor growth through an H19-mediated Wnt/β-catenin signaling regulatory axis in OS cells. The translational potential of this article The information gained from this study provides a novel underlying mechanism of GA mediated anti-OS activity, suggesting that GA may be a promising drug candidate for OS patients.
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Key Words
- CD44, cluster of differentiation 44
- GA, gallic acid
- Gallic acid
- H19
- IHC, Immunohistochemistry
- LncRNAs, long noncoding RNAs
- Metastasis
- Myc, Cellular-myelocytomatosis viral oncogene
- OS, osteosarcoma
- Oct3/4, POU class 5 homeobox 1
- Osteosarcoma
- PI, propidium iodide
- RIPA, Radio Immunoprecipitation Assay
- TCM, traditional Chinese medicine
- Wnt/β-catenin signaling
- pBabe, the empty lasmids
- pH19, H19 overexpression plasmids
- qRT-PCR, Quantitative reverse-transcription polymerase chain reaction
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Affiliation(s)
- Fengxiang Pang
- Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China,The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Shouchang Ding
- Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China,The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Nan Li
- Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China,The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Zhipeng Li
- Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China,The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Nannan Tian
- Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China,The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Chuanjian Shi
- School of Pharmaceutical Sciences, Southern Medical University,Guangzhou, Guangdong, 511458, China
| | - Fengwei Zhang
- Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China,The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Yongxin Mai
- Key Laboratory of Orthopaedics and Traumatology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China,The First Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510405, China
| | - Jinfang Zhang
- Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine, China,Corresponding author. Shenzhen Hospital (Futian) of Guangzhou University of Chinese Medicine.
| | - Junyan Wang
- School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong, 510006, China,Corresponding author. School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou 510006, China.
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13
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Ngum JA, Tatang FJ, Toumeni MH, Nguengo SN, Simo USF, Mezajou CF, Kameni C, Ngongang NN, Tchinda MF, Dongho Dongmo FF, Akami M, Ngane Ngono AR, Tamgue O. An overview of natural products that modulate the expression of non-coding RNAs involved in oxidative stress and inflammation-associated disorders. Front Pharmacol 2023; 14:1144836. [PMID: 37168992 PMCID: PMC10165025 DOI: 10.3389/fphar.2023.1144836] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2023] [Accepted: 03/24/2023] [Indexed: 05/13/2023] Open
Abstract
Oxidative stress is a state in which oxidants are produced in excess in the body's tissues and cells, resulting in a biological imbalance amid the generation of reactive oxygen and nitrogen species (RONS) from redox reactions. In case of insufficient antioxidants to balance, the immune system triggers signaling cascades to mount inflammatory responses. Oxidative stress can have deleterious effects on major macromolecules such as lipids, proteins, and nucleic acids, hence, Oxidative stress and inflammation are among the multiple factors contributing to the etiology of several disorders such as diabetes, cancers, and cardiovascular diseases. Non-coding RNAs (ncRNAs) which were once referred to as dark matter have been found to function as key regulators of gene expression through different mechanisms. They have dynamic roles in the onset and development of inflammatory and oxidative stress-related diseases, therefore, are potential targets for the control of those diseases. One way of controlling those diseases is through the use of natural products, a rich source of antioxidants that have drawn attention with several studies showing their involvement in combating chronic diseases given their enormous gains, low side effects, and toxicity. In this review, we highlighted the natural products that have been reported to target ncRNAs as mediators of their biological effects on oxidative stress and several inflammation-associated disorders. Those natural products include Baicalein, Tanshinone IIA, Geniposide, Carvacrol/Thymol, Triptolide, Oleacein, Curcumin, Resveratrol, Solarmargine, Allicin, aqueous extract or pulp of Açai, Quercetin, and Genistein. We also draw attention to some other compounds including Zanthoxylum bungeanum, Canna genus rhizome, Fuzi-ganjiang herb pair, Aronia melanocarpa, Peppermint, and Gingerol that are effective against oxidative stress and inflammation-related disorders, however, have no known effect on ncRNAs. Lastly, we touched on the many ncRNAs that were found to play a role in oxidative stress and inflammation-related disorders but have not yet been investigated as targets of a natural product. Shedding more light into these two last points of shadow will be of great interest in the valorization of natural compounds in the control and therapy of oxidative stress- and inflammation-associated disorders.
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14
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Hayakawa S, Ohishi T, Oishi Y, Isemura M, Miyoshi N. Contribution of Non-Coding RNAs to Anticancer Effects of Dietary Polyphenols: Chlorogenic Acid, Curcumin, Epigallocatechin-3-Gallate, Genistein, Quercetin and Resveratrol. Antioxidants (Basel) 2022; 11:antiox11122352. [PMID: 36552560 PMCID: PMC9774417 DOI: 10.3390/antiox11122352] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2022] [Revised: 11/18/2022] [Accepted: 11/24/2022] [Indexed: 11/29/2022] Open
Abstract
Growing evidence has been accumulated to show the anticancer effects of daily consumption of polyphenols. These dietary polyphenols include chlorogenic acid, curcumin, epigallocatechin-3-O-gallate, genistein, quercetin, and resveratrol. These polyphenols have similar chemical and biological properties in that they can act as antioxidants and exert the anticancer effects via cell signaling pathways involving their reactive oxygen species (ROS)-scavenging activity. These polyphenols may also act as pro-oxidants under certain conditions, especially at high concentrations. Epigenetic modifications, including dysregulation of noncoding RNAs (ncRNAs) such as microRNAs, long noncoding RNAs, and circular RNAs are now known to be involved in the anticancer effects of polyphenols. These polyphenols can modulate the expression/activity of the component molecules in ROS-scavenger-triggered anticancer pathways (RSTAPs) by increasing the expression of tumor-suppressive ncRNAs and decreasing the expression of oncogenic ncRNAs in general. Multiple ncRNAs are similarly modulated by multiple polyphenols. Many of the targets of ncRNAs affected by these polyphenols are components of RSTAPs. Therefore, ncRNA modulation may enhance the anticancer effects of polyphenols via RSTAPs in an additive or synergistic manner, although other mechanisms may be operating as well.
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Affiliation(s)
- Sumio Hayakawa
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan
- Correspondence: (S.H.); (N.M.); Tel.: +81-3-3822-2131 (S.H.); +81-54-264-5531 (N.M.)
| | - Tomokazu Ohishi
- Institute of Microbial Chemistry (BIKAKEN), Numazu, Microbial Chemistry Research Foundation, Shizuoka 410-0301, Japan
- Institute of Microbial Chemistry (BIKAKEN), Laboratory of Oncology, Microbial Chemistry Research Foundation, Shinagawa-ku, Tokyo 141-0021, Japan
| | - Yumiko Oishi
- Department of Biochemistry and Molecular Biology, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo 113-8602, Japan
| | - Mamoru Isemura
- Tea Science Center, University of Shizuoka, Shizuoka 422-8526, Japan
| | - Noriyuki Miyoshi
- Graduate School of Integrated Pharmaceutical and Nutritional Sciences, University of Shizuoka, Shizuoka 422-8526, Japan
- Correspondence: (S.H.); (N.M.); Tel.: +81-3-3822-2131 (S.H.); +81-54-264-5531 (N.M.)
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15
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Zhai W, Hu Y, Zhang Y, Zhang G, Chen H, Tan X, Zheng Y, Gao W, Wei Y, Wu J. A systematic review of phytochemicals from Chinese herbal medicines for non-coding RNAs-mediated cancer prevention and treatment: From molecular mechanisms to potential clinical applications. MEDICINE IN NOVEL TECHNOLOGY AND DEVICES 2022. [DOI: 10.1016/j.medntd.2022.100192] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022] Open
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16
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Mohapatra P, Chandrasekaran N. Wnt/β-catenin targeting in liver carcinoma through nanotechnology-based drug repurposing: A review. Biomed Pharmacother 2022; 155:113713. [PMID: 36126453 DOI: 10.1016/j.biopha.2022.113713] [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: 08/11/2022] [Revised: 09/08/2022] [Accepted: 09/15/2022] [Indexed: 11/16/2022] Open
Abstract
Liver cancer is the fifth most widespread in the world, with a high fatality rate and poor prognosis.However,surgicalresction,thermal/radiofrequencyablation,chemo/radioembolization and pathway targeting to the cancer cells are all possible options for treating Liver Carcinoma. Unfortunately, once the tumour has developed and spread, diagnosis often occurs too late. The targeted therapy has demonstrated notable, albeit modest, efficacy in some patients with advanced HCC. This demonstrates the necessity of creating additional focused treatments and, in pursuit of this end, the need to find ever-more pathways as prospective targets. Despite the critical need, there are currently no Wnt signalling directed therapy on the research field, only a few methods have progressed beyond the early stage of clinical studies. In the present study, we report that repurposing of drug previously licensed for other diseases is one possible strategy inhibit malignant cell proliferation and renewal by removing individuals protein expression in the Wnt/β-catenin pathway. Particularly β-catenin complex is present in Liver cancer, where tumour necrosis factor is indispensable for the complex formation and β-catenin interactions are disrupted upon drug in nano-carrier through nanotechnology. This study findings not only highlight that repurposing drug could improve liver cancer treatment outcomes but also focused to character traits and functions of the Wnt signalling cascade's molecular targets and how they could be used to get anti-tumour results method to targeting Wnt/β-catenin in liver carcinoma.
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17
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Xie W, Chu M, Song G, Zuo Z, Han Z, Chen C, Li Y, Wang ZW. Emerging roles of long noncoding RNAs in chemoresistance of pancreatic cancer. Semin Cancer Biol 2022; 83:303-318. [PMID: 33207266 DOI: 10.1016/j.semcancer.2020.11.004] [Citation(s) in RCA: 76] [Impact Index Per Article: 25.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2020] [Revised: 11/04/2020] [Accepted: 11/05/2020] [Indexed: 02/08/2023]
Abstract
Pancreatic cancer is one of the most common causes of cancer death in the world due to the lack of early symptoms, metastasis occurrence and chemoresistance. Therefore, early diagnosis by detection of biomarkers, blockade of metastasis, and overcoming chemoresistance are the effective strategies to improve the survival of pancreatic cancer patients. Accumulating evidence has revealed that long noncoding RNA (lncRNA) and circular RNAs (circRNAs) play essential roles in modulating chemosensitivity in pancreatic cancer. In this review article, we will summarize the role of lncRNAs in drug resistance of pancreatic cancer cells, including HOTTIP, HOTAIR, PVT1, linc-ROR, GAS5, UCA1, DYNC2H1-4, MEG3, TUG1, HOST2, HCP5, SLC7A11-AS1 and CASC2. We also highlight the function of circRNAs, such as circHIPK3 and circ_0000284, in regulation of drug sensitivity of pancreatic cancer cells. Moreover, we describe a number of compounds, including curcumin, genistein, resveratrol, quercetin, and salinomycin, which may modulate the expression of lncRNAs and enhance chemosensitivity in pancreatic cancers. Therefore, targeting specific lncRNAs and cicrRNAs could contribute to reverse chemoresistance of pancreatic cancer cells. We hope this review might stimulate the studies of lncRNAs and cicrRNAs, and develop the new therapeutic strategy via modulating these noncoding RNAs to promote chemosensitivity of pancreatic cancer cells.
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Affiliation(s)
- Wangkai Xie
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Man Chu
- Center of Scientific Research, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China
| | - Gendi Song
- Center of Scientific Research, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China
| | - Ziyi Zuo
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Zheng Han
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Chenbin Chen
- Department of Gastrointestinal Surgery, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, 325027, China
| | - Yuyun Li
- Bengbu Medical College Key Laboratory of Cancer Research and Clinical Laboratory Diagnosis, School of Laboratory Medicine, Bengbu Medical College, Anhui, 233030, China.
| | - Zhi-Wei Wang
- Center of Scientific Research, the Second Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325027, Zhejiang, China.
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18
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Katoch S, Sharma V, Patial V. Peroxisome proliferator-activated receptor gamma as a therapeutic target for hepatocellular carcinoma: Experimental and clinical scenarios. World J Gastroenterol 2022; 28:3535-3554. [PMID: 36161051 PMCID: PMC9372809 DOI: 10.3748/wjg.v28.i28.3535] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/17/2022] [Revised: 04/25/2022] [Accepted: 06/24/2022] [Indexed: 02/06/2023] Open
Abstract
Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Viral hepatitis is a significant risk factor for HCC, although metabolic syndrome and diabetes are more frequently associated with the HCC. With increasing prevalence, there is expected to be > 1 million cases annually by 2025. Therefore, there is an urgent need to establish potential therapeutic targets to cure this disease. Peroxisome-proliferator-activated receptor gamma (PPARγ) is a ligand-activated transcription factor that plays a crucial role in the patho-physiology of HCC. Many synthetic agonists of PPARγ suppress HCC in experimental studies and clinical trials. These synthetic agonists have shown promising results by inducing cell cycle arrest and apoptosis in HCC cells and preventing the invasion and metastasis of HCC. However, some synthetic agonists also pose severe side effects in addition to their therapeutic efficacy. Thus natural PPARγ agonists can be an alternative to exploit this potential target for HCC treatment. In this review, the regulatory role of PPARγ in the pathogenesis of HCC is elucidated. Furthermore, the experimental and clinical scenario of both synthetic and natural PPARγ agonists against HCC is discussed. Most of the available literature advocates PPARγ as a potential therapeutic target for the treatment of HCC.
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Affiliation(s)
- Swati Katoch
- Division of Dietetics and Nutrition Technology, Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India
- Academy of Scientific and Innovative Research, Ghaziabad 201002, UP, India
| | - Vinesh Sharma
- Division of Dietetics and Nutrition Technology, Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India
- Academy of Scientific and Innovative Research, Ghaziabad 201002, UP, India
| | - Vikram Patial
- Division of Dietetics and Nutrition Technology, Institute of Himalayan Bioresource Technology, Palampur 176061, Himachal Pradesh, India
- Academy of Scientific and Innovative Research, Ghaziabad 201002, UP, India
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19
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Xu Y, Yu X, Sun Z, He Y, Guo W. Roles of lncRNAs Mediating Wnt/β-Catenin Signaling in HCC. Front Oncol 2022; 12:831366. [PMID: 35356220 PMCID: PMC8959654 DOI: 10.3389/fonc.2022.831366] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 02/14/2022] [Indexed: 11/18/2022] Open
Abstract
Hepatocellular carcinoma (HCC) is considered the second most deadly cancer worldwide. Due to the absence of early diagnostic markers and effective therapeutic approaches, distant metastasis and increasing recurrence rates are major difficulties in the clinical treatment of HCC. Further understanding of its pathogenesis has become an urgent goal in HCC research. Recently, abnormal expression of long noncoding RNAs (lncRNAs) was identified as a vital regulator involved in the initiation and development of HCC. Activation of the Wnt/β-catenin pathway has been reported to obviously impact cell proliferation, invasion, and migration of HCC. This article reviews specific interactions, significant mechanisms and molecules related to HCC initiation and progression to provide promising strategies for treatment.
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Affiliation(s)
- Yating Xu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation Medicine, Zhengzhou, China
| | - Xiao Yu
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation Medicine, Zhengzhou, China
| | - Zongzong Sun
- Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China
| | - Yuting He
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation Medicine, Zhengzhou, China
| | - Wenzhi Guo
- Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.,Open and Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation at Henan Universities, Zhengzhou, China.,Zhengzhou Key Laboratory of Hepatobiliary & Pancreatic Diseases and Organ Transplantation Medicine, Zhengzhou, China
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20
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Curcumin Inhibits Papillary Thyroid Cancer Cell Proliferation by Regulating lncRNA LINC00691. Anal Cell Pathol 2022; 2022:5946670. [PMID: 35256924 PMCID: PMC8898135 DOI: 10.1155/2022/5946670] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2021] [Revised: 02/07/2022] [Accepted: 02/13/2022] [Indexed: 12/19/2022] Open
Abstract
Papillary thyroid cancer (PTC) is a type of epithelial-derived differentiated TC that reportedly accounts for a majority of TCs. Curcumin, a polyphenolic compound and a member of the Zingiberaceae (ginger) family derived from turmeric plants, can exhibit anticancer effects. Herein, we aimed to investigate the effect of curcumin on PTC and elucidate underlying mechanisms. Accordingly, PTC B-CPAP cells were treated with curcumin, in combination with/without long noncoding RNA LINC00691 inhibition, to determine the effect of curcumin and its relationship with LINC00691 in PTC cells. We observed that curcumin treatment decreased B-CPAP cell proliferation and promoted apoptosis. Curcumin inhibited LINC00691 expression in B-CPAP cells. Curcumin administration or si-LINC00691 transfection alone promoted ATP levels, inhibited glucose uptake and lactic acid levels, and inhibited lactate dehydrogenase A and hexokinase 2 protein expression in B-CPAP cells, which were further enhanced by combination treatment. Moreover, curcumin administration or si-LINC00691 transfection alone inhibited p-Akt activity, further suppressed by combination treatment. Akt inhibition promoted apoptosis and suppressed the Warburg effect in B-CPAP cells. In conclusion, our findings indicate that curcumin promotes apoptosis and suppresses proliferation and the Warburg effect by inhibiting LINC00691 in B-CPAP cells. The precise molecular mechanism might be mediated through the Akt signaling pathway, providing a theoretical basis for the treatment of PTC with curcumin.
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21
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The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation. Cell Mol Biol Lett 2022; 27:7. [PMID: 35033019 PMCID: PMC8903542 DOI: 10.1186/s11658-021-00305-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/08/2021] [Accepted: 12/29/2021] [Indexed: 02/07/2023] Open
Abstract
Canonical Wnt/β-catenin signaling is a complex cell-communication mechanism that has a central role in the progression of various cancers. The cellular factors that participate in the regulation of this signaling are still not fully elucidated. Lysine acetylation is a significant protein modification which facilitates reversible regulation of the target protein function dependent on the activity of lysine acetyltransferases (KATs) and the catalytic function of lysine deacetylases (KDACs). Protein lysine acetylation has been classified into histone acetylation and non-histone protein acetylation. Histone acetylation is a kind of epigenetic modification, and it can modulate the transcription of important biological molecules in Wnt/β-catenin signaling. Additionally, as a type of post-translational modification, non-histone acetylation directly alters the function of the core molecules in Wnt/β-catenin signaling. Conversely, this signaling can regulate the expression and function of target molecules based on histone or non-histone protein acetylation. To date, various inhibitors targeting KATs and KDACs have been discovered, and some of these inhibitors exert their anti-tumor activity via blocking Wnt/β-catenin signaling. Here, we discuss the available evidence in understanding the complicated interaction of protein lysine acetylation with Wnt/β-catenin signaling, and lysine acetylation as a new target for cancer therapy via controlling this signaling.
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22
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Ruiz-Manriquez LM, Estrada-Meza C, Benavides-Aguilar JA, Ledesma-Pacheco SJ, Torres-Copado A, Serrano-Cano FI, Bandyopadhyay A, Pathak S, Chakraborty S, Srivastava A, Sharma A, Paul S. Phytochemicals mediated modulation of microRNAs and long non-coding RNAs in cancer prevention and therapy. Phytother Res 2021; 36:705-729. [PMID: 34932245 DOI: 10.1002/ptr.7338] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 10/07/2021] [Accepted: 11/04/2021] [Indexed: 12/15/2022]
Abstract
MicroRNAs (miRNAs) and long noncoding RNAs (lncRNAs) are two main categories of noncoding RNAs (ncRNAs) that can influence essential biological functions in various ways, as well as their expression and function are tightly regulated in physiological homeostasis. Additionally, the dysregulation of these ncRNAs seems to be crucial to the pathogenesis of human diseases. The latest findings indicate that ncRNAs execute vital roles in cancer initiation and progression, and the cancer phenotype can be reversed by modulating their expression. Available scientific discoveries suggest that phytochemicals such as polyphenols, alkaloids, terpenoids, and organosulfur compounds can significantly modulate multiple cancer-associated miRNAs and lncRNAs, thereby inhibiting cancer initiation and development. However, despite promising outcomes of experimental research, only a few clinical trials are currently being conducted to evaluate the therapeutic effectiveness of these compounds. Nevertheless, understanding phytochemical-mediated ncRNA regulation in cancer and the underlying molecular mechanisms on tumor pathophysiology can aid in the development of novel therapeutic strategies to combat this deadly disease.
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Affiliation(s)
- Luis M Ruiz-Manriquez
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, San Pablo, Mexico
| | - Carolina Estrada-Meza
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, San Pablo, Mexico
| | | | - S Janin Ledesma-Pacheco
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, San Pablo, Mexico
| | - Andrea Torres-Copado
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, San Pablo, Mexico
| | - Francisco I Serrano-Cano
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, San Pablo, Mexico
| | - Anindya Bandyopadhyay
- C4 Rice Center, International Rice Research Institute, Manila, Philippines.,Synthetic Biology, Biofuel and Genome Editing R&D, Reliance Industries Ltd, Navi Mumbai, India
| | - Surajit Pathak
- Department of Medical Biotechnology, Faculty of Allied Health Sciences, Chettinad Hospital and Research Institute (CHRI), Chettinad Academy of Research and Education (CARE), Kelambakkam, Chennai, India
| | - Samik Chakraborty
- Division of Nephrology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts, USA
| | | | - Ashutosh Sharma
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, San Pablo, Mexico
| | - Sujay Paul
- Tecnologico de Monterrey, School of Engineering and Sciences, Campus Queretaro, San Pablo, Mexico
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Homayoonfal M, Asemi Z, Yousefi B. Targeting long non coding RNA by natural products: Implications for cancer therapy. Crit Rev Food Sci Nutr 2021:1-29. [PMID: 34783279 DOI: 10.1080/10408398.2021.2001785] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
In spite of achieving substantial progress in its therapeutic strategies, cancer-associated prevalence and mortality are persistently rising globally. However, most malignant cancers either cannot be adequately diagnosed at the primary phase or resist against multiple treatments such as chemotherapy, surgery, radiotherapy as well as targeting therapy. In recent decades, overwhelming evidences have provided more convincing words on the undeniable roles of long non-coding RNAs (lncRNAs) in incidence and development of various cancer types. Recently, phytochemical and nutraceutical compounds have received a great deal of attention due to their inhibitory and stimulatory effects on oncogenic and tumor suppressor lncRNAs respectively that finally may lead to attenuate various processes of cancer cells such as growth, proliferation, metastasis and invasion. Therefore, application of phytochemicals with anticancer characteristics can be considered as an innovative approach for treating cancer and increasing the sensitivity of cancer cells to standard prevailing therapies. The purpose of this review was to investigate the effect of various phytochemicals on regulation of lncRNAs in different human cancer and evaluate their capabilities for cancer treatment and prevention.
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Affiliation(s)
- Mina Homayoonfal
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, I.R. Iran
| | - Zatollah Asemi
- Research Center for Biochemistry and Nutrition in Metabolic Diseases, Institute for Basic Sciences, Kashan University of Medical Sciences, Kashan, I.R. Iran
| | - Bahman Yousefi
- Molecular Medicine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.,Department of Biochemistry, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran
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24
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Zhou F, Hu X, Feng W, Li M, Yu B, Fu C, Ou C. LncRNA H19 abrogates the protective effects of curcumin on rat carotid balloon injury via activating Wnt/β-catenin signaling pathway. Eur J Pharmacol 2021; 910:174485. [PMID: 34487706 DOI: 10.1016/j.ejphar.2021.174485] [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: 01/31/2021] [Revised: 08/28/2021] [Accepted: 09/02/2021] [Indexed: 11/19/2022]
Abstract
Intimal hyperplasia-induced restenosis is a common response to vascular endothelial damage caused by mechanical force or other stimulation, and is closely linked to vascular remodeling. Curcumin, a traditional Chinese medicine, exhibits potent protective effects in cardiovascular diseases; for example, it attenuates vascular remodeling. Although the suppressive effects of curcumin on diseases caused by vascular narrowing have been investigated, the underlying mechanisms remain unknown. Long non-coding RNAs (lncRNAs) regulate various pathological processes and affect the action of drugs. In the present study, we found that the curcumin remarkably downregulated the expression of lncRNA H19 and thereby inhibited intimal hyperplasia-induced vascular restenosis. Furthermore, the inhibition of the expression of H19 by curcumin resulted in the inactivation of the Wnt/β-catenin signaling. Overall, we show that curcumin suppresses intimal hyperplasia via the H19/Wnt/β-catenin pathway, implying that H19 is a critical molecule in the suppression of intimal hyperplasia after balloon injury by curcumin. These insights should be useful for potential application of curcumin as a therapeutic intervention in vascular stenosis.
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Affiliation(s)
- Feiran Zhou
- Department of Cardiology, Laboratory of Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, 510515, China
| | - Xinyi Hu
- Department of Cardiology, Laboratory of Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, 510515, China
| | - Weijing Feng
- Department of Cardiology, Laboratory of Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China; Department of Cardiology, State Key Laboratory of Organ Failure Research, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, 510515, China
| | - Minghui Li
- Department of Cardiology, Laboratory of Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, 510515, China
| | - Bin Yu
- Department of Cardiology, Laboratory of Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, 510515, China
| | - Chenxing Fu
- Department of Cardiology, Laboratory of Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, 510515, China
| | - Caiwen Ou
- Department of Cardiology, Laboratory of Heart Center, Guangdong Provincial Biomedical Engineering Technology Research Center for Cardiovascular Disease, Zhujiang Hospital, Southern Medical University, Guangzhou, 510515, China; Guangdong Provincial Key Laboratory of Shock and Microcirculation, Guangzhou, 510515, China.
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25
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Khan H, Ni Z, Feng H, Xing Y, Wu X, Huang D, Chen L, Niu Y, Shi G. Combination of curcumin with N-n-butyl haloperidol iodide inhibits hepatocellular carcinoma malignant proliferation by downregulating enhancer of zeste homolog 2 (EZH2) - lncRNA H19 to silence Wnt/β-catenin signaling. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 91:153706. [PMID: 34517264 DOI: 10.1016/j.phymed.2021.153706] [Citation(s) in RCA: 16] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/06/2021] [Revised: 08/09/2021] [Accepted: 08/10/2021] [Indexed: 02/05/2023]
Abstract
BACKGROUND Hepatocellular carcinoma (HCC) is one of the most common cause of cancer-related death worldwide. Curcumin (C) has been extensively investigated in different types of malignancies, including hepatocellular carcinoma, but its physicochemical properties have significantly influenced its clinical use. Several approaches are being explored to enhance curcumin's therapeutic response, including its combination with various drugs. PURPOSE This study aimed to evaluate the anti-tumor effect of curcumin (C) in combination with F2 (N-n-butyl haloperidol iodide) on hepatocellular carcinoma and its potential underlying mechanism in vitro and in vivo. METHODS Cell proliferation was evaluated by CCK-8 and colony formation assays, and apoptosis was measured by flow cytometry. The migratory and invasive abilities of Hep3B and SMMC-7721 cells were measured by wound-healing and matrigel transwell assays. In order to investigate the molecular pathways, various experiments such as western blotting, qPCR, RNA-seq, immunostaining and transfection were performed. To evaluate the anti-HCC effects in vivo, a xenograft tumor model was used. RESULTS Our findings showed that the combination of curcumin (C) & F2 (F2C) strongly inhibited malignant proliferation and migration in SMMC-7721 and Hep3B cells. The F2C treatment downregulates enhancer of zeste homolog 2 (EZH2) transcription and protein expression, which is key epigenetic regulator responsible for HCC development. Moreover, the inhibition of EZH2 by F2C led to Wnt/β-catenin signaling inhibition by decreasing tri-methylation of histone H3 at lysine 27 (H3K27me3) and long non-coding RNA H19 expression. The inhibition of F2C was associated with the suppression of tumorigenicity in xenograft HCC models. CONCLUSION These findings suggested that, F2C inhibited HCC formation, migration and its modulatory mechanism seemed to be associated with downregulation of EZH2, silencing Wnt/β-catenin signaling by interacting with H19, suggesting that F2C may be a promising drug in the clinical treatment of HCC.
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Affiliation(s)
- Hanif Khan
- Department of Pharmacology, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong, China
| | - Zhengzhong Ni
- Department of Pharmacology, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong, China
| | - Hai Feng
- Shanghai Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Yaqi Xing
- Department of Pharmacology, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong, China
| | - Xuejun Wu
- Department of Pharmacology, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong, China
| | - Danmei Huang
- Department of Pharmacology, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong, China
| | - Ling Chen
- Department of Pharmacology, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong, China
| | - Yongdong Niu
- Department of Pharmacology, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong, China.
| | - Ganggang Shi
- Department of Pharmacology, Shantou University Medical College, No. 22 Xinling Road, Shantou 515041, Guangdong, China.
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26
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Shah D, Gandhi M, Kumar A, Cruz-Martins N, Sharma R, Nair S. Current insights into epigenetics, noncoding RNA interactome and clinical pharmacokinetics of dietary polyphenols in cancer chemoprevention. Crit Rev Food Sci Nutr 2021; 63:1755-1791. [PMID: 34433338 DOI: 10.1080/10408398.2021.1968786] [Citation(s) in RCA: 33] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Several studies have reported the health-beneficial effects of dietary phytochemicals, namely polyphenols, to prevent various diseases, including cancer. Polyphenols, like (-)-epigallocatechin-3-gallate (EGCG) from green tea, curcumin from turmeric, and ellagic acid from pomegranate are known to act by modulating antioxidant, anti-inflammatory and apoptotic signal transduction pathways in the tumor milieu. The evolving literature underscores the role of epigenetic regulation of genes associated with cancer by these polyphenols, primarily via non-coding RNAs (ncRNAs), such as microRNAs (miRNA) and long noncoding RNA (lncRNA). However, there is little clarity on the exact role(s) played by these ncRNAs and their interactions with other ncRNAs, or with their protein targets, in response to modulation by these dietary polyphenols. Here, we review ncRNA interactions and functional networks of the complex ncRNA interactome with their targets in preclinical studies along with the role of epigenetics as well as key aspects of pharmacokinetics and phytochemistry of dietary polyphenols. We also summarize the current state of clinical trials with these dietary polyphenols. Taken together, this synthetic review provides insights into the molecular aspects underlying the anticancer chemopreventive effects of dietary polyphenols as well as summarizes data on novel biomarkers modulated by these polyphenols for preventive or therapeutic purposes in various types of cancer.
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Affiliation(s)
| | | | - Arun Kumar
- Division of Radiation Biosciences, Institute of Nuclear Medicine and Allied Sciences, Defence Research and Development Organization, Timarpur Delhi, India
| | - Natália Cruz-Martins
- Faculty of Medicine, University of Porto, Porto, Portugal.,Institute for research and Innovation in Health (i3S), University of Porto, Porto, Portugal.,Institute of Research and Advanced Training in Health Sciences and Technologies (CESPU), Gandra PRD, Portugal
| | - Rohit Sharma
- Department of Rasa Shastra and Bhaishajya Kalpana, Faculty of Ayurveda, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India
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27
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Gowhari Shabgah A, Hejri Zarifi S, Mazloumi Kiapey SS, Ezzatifar F, Pahlavani N, Soleimani D, Mohammadian Haftcheshmeh S, Mohammadi H, Gholizadeh Navashenaq J. Curcumin and cancer; are long non-coding RNAs missing link? PROGRESS IN BIOPHYSICS AND MOLECULAR BIOLOGY 2021; 164:63-71. [PMID: 33894206 DOI: 10.1016/j.pbiomolbio.2021.04.001] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 03/08/2021] [Accepted: 04/15/2021] [Indexed: 02/08/2023]
Abstract
Despite significant signs of progress in cancer treatment over the past decade, either cancer prevalence or mortality continuously grow worldwide. Current anti-cancer agents show insignificant effectiveness, followed by serious side effects. It is important to find new, highly efficient pharmacological agents to increase cancer patients' clinical outcomes. Curcumin, a polyphenolic compound, has gained growing attention because of its anti-cancer properties. Curcumin can hinder the development, migration, and metastasis of cancer cells. The anti-cancer effects of curcumin are principally attributed to the regulation of several cellular signaling pathways, including MAPK/PI3K/Akt, Wnt/β-catenin, JAK/STAT, and NF-ĸB signaling pathways. Furthermore, curcumin can affect the expression and function of tumor-suppressive and oncogenic long non-coding RNAs (lncRNAs). In this study, we briefly reviewed the modulatory effect of curcumin on dysregulated tumor-supportive and tumor-suppressive lncRNAs in several cancers. It is hoped that a better understanding of curcumin's anti-cancer properties would pave the way for the development of a therapeutic approach in cancer.
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Affiliation(s)
| | - Sudiyeh Hejri Zarifi
- Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | | | - Fatemeh Ezzatifar
- Molecular and Cell Biology Research Center, Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran; Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran
| | - Naseh Pahlavani
- Social Development and Health Promotion Research Center, Gonabad University of Medical Sciences, Gonabad, Iran; Cellular and Molecular Research Center, Research Institute for Health Development, Kurdistan University of Medical Sciences, Sanandaj, Iran
| | - Davood Soleimani
- Department of Nutritional Sciences, School of Nutrition Sciences and Food Technology, Kermanshah University of Medical Sciences, Kermanshah, Iran
| | - Saeed Mohammadian Haftcheshmeh
- Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran; Students Research Committee, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Hamed Mohammadi
- Non-Communicable Diseases Research Center, Alborz University of Medical Sciences, Karaj, Iran; Department of Immunology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran
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28
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Wang H, Zhang K, Liu J, Yang J, Tian Y, Yang C, Li Y, Shao M, Su W, Song N. Curcumin Regulates Cancer Progression: Focus on ncRNAs and Molecular Signaling Pathways. Front Oncol 2021; 11:660712. [PMID: 33912467 PMCID: PMC8072122 DOI: 10.3389/fonc.2021.660712] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2021] [Accepted: 03/24/2021] [Indexed: 12/24/2022] Open
Abstract
Curcumin [(1E,6E) ‑1,7‑bis(4‑hydroxy‑3‑methoxyphenyl) hepta‑1,6‑diene‑3,5‑ dione] is a natural polyphenol derived from the rhizome of the turmeric plant Curcuma longa. Accumulated evidences have presented curcumin’s function in terms of anti-inflammatory, antioxidant properties, and especially anti-tumor activities. Studies demonstrated that curcumin could exert anti-tumor activity via multiple biological signaling pathways, such as PI3K/Akt, JAK/STAT, MAPK, Wnt/β-catenin, p53, NF-ĸB and apoptosis related signaling pathways. Moreover, Curcumin can inhibit tumor proliferation, angiogenesis, epithelial-mesenchymal transition (EMT), invasion and metastasis by regulating tumor related non-coding RNA (ncRNA) expression. In this review, we summarized the roles of curcumin in regulating signaling pathways and ncRNAs in different kinds of cancers. We also discussed the regulatory effect of curcumin through inhibiting carcinogenic miRNA and up regulating tumor suppressive miRNA. Furthermore, we aim to illustrate the cross regulatory relationship between ncRNA and signaling pathways, further to get a better understanding of the anti-tumor mechanism of curcumin, thus lay a theoretical foundation for the clinical application of curcumin in the future.
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Affiliation(s)
- Haijun Wang
- Department of Pathology, Key Laboratory of Clinical Molecular Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.,School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Ke Zhang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Jia Liu
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Jie Yang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Yidan Tian
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Chen Yang
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Yushan Li
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China
| | - Minglong Shao
- Department of Mental Health, The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Wei Su
- Department of Pathology, Key Laboratory of Clinical Molecular Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, China
| | - Na Song
- School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.,Institute of Precision Medicine, Xinxiang Medical University, Xinxiang, China
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