Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin
Romidepsin, also known as NSC630176, FR901228, FK-228, FR-901228, depsipeptide, or Istodax®, is a natural molecule produced by the Chromobacterium violaceum bacterium that has been approved for its anti-cancer effect. This compound is a selective histone deacetylase (HDAC) inhibitor, which modifies...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332223005632 |
| _version_ | 1797801868984844288 |
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| author | Nasreddine El Omari Learn-Han Lee Saad Bakrim Hafiz A. Makeen Hassan A. Alhazmi Syam Mohan Asaad Khalid Long Chiau Ming Abdelhakim Bouyahya |
| author_facet | Nasreddine El Omari Learn-Han Lee Saad Bakrim Hafiz A. Makeen Hassan A. Alhazmi Syam Mohan Asaad Khalid Long Chiau Ming Abdelhakim Bouyahya |
| author_sort | Nasreddine El Omari |
| collection | DOAJ |
| description | Romidepsin, also known as NSC630176, FR901228, FK-228, FR-901228, depsipeptide, or Istodax®, is a natural molecule produced by the Chromobacterium violaceum bacterium that has been approved for its anti-cancer effect. This compound is a selective histone deacetylase (HDAC) inhibitor, which modifies histones and epigenetic pathways. An imbalance between HDAC and histone acetyltransferase can lead to the down-regulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by romidepsin indirectly contributes to the anticancer therapeutic effect by causing the accumulation of acetylated histones, restoring normal gene expression in cancer cells, and promoting alternative pathways, including the immune response, p53/p21 signaling cascades, cleaved caspases, poly (ADP-ribose) polymerase (PARP), and other events. Secondary pathways mediate the therapeutic action of romidepsin by disrupting the endoplasmic reticulum and proteasome and/or aggresome, arresting the cell cycle, inducing intrinsic and extrinsic apoptosis, inhibiting angiogenesis, and modifying the tumor microenvironment. This review aimed to highlight the specific molecular mechanisms responsible for HDAC inhibition by romidepsin. A more detailed understanding of these mechanisms can significantly improve the understanding of cancer cell disorders and pave the way for new therapeutic approaches using targeted therapy. |
| first_indexed | 2024-03-13T04:57:04Z |
| format | Article |
| id | doaj.art-d1da66ffb0ad4dd580886e8d305c06bf |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-03-13T04:57:04Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-d1da66ffb0ad4dd580886e8d305c06bf2023-06-18T05:00:34ZengElsevierBiomedicine & Pharmacotherapy0753-33222023-08-01164114774Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsinNasreddine El Omari0Learn-Han Lee1Saad Bakrim2Hafiz A. Makeen3Hassan A. Alhazmi4Syam Mohan5Asaad Khalid6Long Chiau Ming7Abdelhakim Bouyahya8Laboratory of Histology, Embryology, and Cytogenetic, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10100, MoroccoNovel Bacteria and Drug Discovery Research Group (NBDD), Microbiome and Bioresource Research Strength (MBRS), Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Malaysia; Corresponding authors.Geo-Bio-Environment Engineering and Innovation Laboratory, Molecular Engineering, Biotechnology and Innovation Team, Polydisciplinary Faculty of Taroudant, Ibn Zohr University, Agadir 80000, MoroccoPharmacy Practice Research Unit, Clinical Pharmacy Department, Faculty of Pharmacy, Jazan University, Jazan, Saudi ArabiaSubstance Abuse and Toxicology Research Center, Jazan University, P.O. Box: 114, Jazan, Saudi Arabia; Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, 45142 Jazan, Saudi ArabiaSubstance Abuse and Toxicology Research Center, Jazan University, P.O. Box: 114, Jazan, Saudi Arabia; School of Health Sciences, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India; Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College, Saveetha In-20 stitute of Medical and Technical Science, Saveetha University, Chennai, IndiaSubstance Abuse and Toxicology Research Center, Jazan University, P.O. Box: 114, Jazan, Saudi Arabia; Medicinal and Aromatic Plants Research Institute, National Center for Research, Khartoum 11111, Sudan; Corresponding author at: Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box: 114, Jazan, Saudi Arabia.School of Medical and Life Sciences, Sunway University, 47500 Sunway City, Malaysia; Corresponding authors.Laboratory of Human Pathologies Biology, Department of Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, MoroccoRomidepsin, also known as NSC630176, FR901228, FK-228, FR-901228, depsipeptide, or Istodax®, is a natural molecule produced by the Chromobacterium violaceum bacterium that has been approved for its anti-cancer effect. This compound is a selective histone deacetylase (HDAC) inhibitor, which modifies histones and epigenetic pathways. An imbalance between HDAC and histone acetyltransferase can lead to the down-regulation of regulatory genes, resulting in tumorigenesis. Inhibition of HDACs by romidepsin indirectly contributes to the anticancer therapeutic effect by causing the accumulation of acetylated histones, restoring normal gene expression in cancer cells, and promoting alternative pathways, including the immune response, p53/p21 signaling cascades, cleaved caspases, poly (ADP-ribose) polymerase (PARP), and other events. Secondary pathways mediate the therapeutic action of romidepsin by disrupting the endoplasmic reticulum and proteasome and/or aggresome, arresting the cell cycle, inducing intrinsic and extrinsic apoptosis, inhibiting angiogenesis, and modifying the tumor microenvironment. This review aimed to highlight the specific molecular mechanisms responsible for HDAC inhibition by romidepsin. A more detailed understanding of these mechanisms can significantly improve the understanding of cancer cell disorders and pave the way for new therapeutic approaches using targeted therapy.http://www.sciencedirect.com/science/article/pii/S0753332223005632RomidepsinTumourP53Histone deacetylase inhibitors (HDACi)Molecular pathwaysEpigenetic |
| spellingShingle | Nasreddine El Omari Learn-Han Lee Saad Bakrim Hafiz A. Makeen Hassan A. Alhazmi Syam Mohan Asaad Khalid Long Chiau Ming Abdelhakim Bouyahya Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin Biomedicine & Pharmacotherapy Romidepsin Tumour P53 Histone deacetylase inhibitors (HDACi) Molecular pathways Epigenetic |
| title | Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin |
| title_full | Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin |
| title_fullStr | Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin |
| title_full_unstemmed | Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin |
| title_short | Molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin |
| title_sort | molecular mechanistic pathways underlying the anticancer therapeutic efficiency of romidepsin |
| topic | Romidepsin Tumour P53 Histone deacetylase inhibitors (HDACi) Molecular pathways Epigenetic |
| url | http://www.sciencedirect.com/science/article/pii/S0753332223005632 |
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