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The Endocannabinoid System, a New Gatekeeper in the Pharmacology of Human Hepatocellular Carcinoma Publisher Pubmed



Ebrahimi N1 ; Far NP2 ; Fakhr SS3 ; Faghihkhorasani F4 ; Miraghel SA5 ; Chaleshtori SR6 ; Rezaeitazangi F7 ; Beiranvand S8 ; Baziyar P9 ; Manavi MS10 ; Zarrabi A11 ; Nabavi N12 ; Ren J13, 14 ; Aref AR15, 16
Authors
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Authors Affiliations
  1. 1. Genetics Division, Department of Cell and Molecular Biology and Microbiology, Faculty of Science and Technology, University of Isfahan, Iran
  2. 2. Department of Microbiology, Faculty of Advanced Science and Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran
  3. 3. Division of Biotechnology, Faculty of Applied Ecology, Agricultural Sciences and Biotechnology, Campus, Hamar, Norway
  4. 4. Medical Campus, Xi'an Jiaotong University, Shaanxi Province, Xi'an, China
  5. 5. Nocivelli Institute for Molecular Medicine, Department of Molecular and Translational Medicine, University of Brescia, Italy
  6. 6. Department of Genetics, Faculty of Basic Sciences, Shahrekord University, Iran
  7. 7. Department of Anatomy, School of Medicine, Fasa University of Medical Sciences, Fasa, Iran
  8. 8. Department of Biotechnology, School of Basic Sciences, Islamic Azad University, Shahrekord Branch, Shahrekord, Iran
  9. 9. Department of Molecular and Cell Biology, Faculty of Basic Science, Uinversity of Mazandaran, Babolsar, Iran
  10. 10. Otolaryngology Department, Tehran University of Medical Science, Tehran, Iran
  11. 11. Department of Biomedical Engineering, Faculty of Engineering and Natural Sciences, Istinye University, Istanbul, 34396, Turkey
  12. 12. Department of Urological Sciences and Vancouver Prostate Centre, University of British Columbia, Vancouver, V6H3Z6, BC, Canada
  13. 13. Department of Cardiology, Zhongshan Hospital Fudan University, Shanghai, 200032, China
  14. 14. Department of Laboratory Medicine and Pathology, University of Washington, 98195, WA, United States
  15. 15. Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, MA, United States
  16. 16. Xsphera Biosciences, Translational Medicine Group, 6 Tide Street, Boston, 02210, MA, United States

Source: Environmental Research Published:2023


Abstract

Despite numerous prevention methodologies and treatment options, hepatocellular carcinoma (HCC) still remains as the third leading life-threatening cancer. It is thus pertinent to develop new treatment modality to fight this devastating carcinoma. Ample recent studies have shown the anti-inflammatory and antitumor roles of the endocannabinoid system in various forms of cancers. Preclinical studies have also confirmed that cannabinoid therapy can be an optimal regimen for cancer treatments. The endocannabinoid system is involved in many cancer-related processes, including induction of endoplasmic reticulum (ER) stress-dependent apoptosis, autophagy, PITRK and ERK signaling pathways, cell invasion, epithelial-mesenchymal transition (EMT), and cancer stem cell (CSC) phenotypes. Moreover, changes in signaling transduction of the endocannabinoid system can be a potential diagnostic and prognostic biomarker for HCC. Due to its pivotal role in lipid metabolism, the endocannabinoid system affects metabolic reprogramming as well as lipid content of exosomes. In addition, due to the importance of non-coding RNAs (ncRNAs), several studies have examined the relationship between microRNAs and the endocannabinoid system in HCC. However, HCC is a pathological condition with high heterogeneity, and therefore using the endocannabinoid system for treatment has faced many controversies. While some studies favored a role of the endocannabinoid system in carcinogenesis and tumor induction, others exhibited the anticancer potential of endocannabinoids in HCC. In this review, specific studies delineating the relationship between endocannabinoids and HCC are examined. Based on collected findings, detailed studies of the molecular mechanism of endocannabinoids as well as preclinical studies for investigating therapeutic or carcinogenic impacts in HCC cancer are strongly suggested. © 2023
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