Stochasticity of anticancer mechanisms underlying clinical effectiveness of vorinostat
Nasreddine El Omari,
Asaad Khalid,
Hafiz A. Makeen,
Hassan A. Alhazmi,
Mohammed Albratty,
Syam Mohan,
Ching Siang Tan,
Long Chiau Ming,
Jack Bee Chook,
Abdelhakim Bouyahya
Affiliations
Nasreddine El Omari
High Institute of Nursing Professions and Health Techniques of Tetouan, Tetouan, Morocco
Asaad Khalid
Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box 114, Postal Code 45142, Jazan, Saudi Arabia; Medicinal and Aromatic Plants Research Institute, National Center for Research, P.O. Box: 2424, Khartoum, 11111, Sudan; Corresponding author. Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box 114, Postal Code 45142, Jazan, Saudi Arabia.
Hafiz A. Makeen
Pharmacy Practice Research Unit, Clinical Pharmacy Department, Faculty of Pharmacy, Jazan University, Jazan, Saudi Arabia
Hassan A. Alhazmi
Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box 114, Postal Code 45142, Jazan, Saudi Arabia; Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, P.O. Box 114, Postal Code 45142, Jazan, Saudi Arabia
Mohammed Albratty
Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, P.O. Box 114, Postal Code 45142, Jazan, Saudi Arabia
Syam Mohan
Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box 114, Postal Code 45142, Jazan, Saudi Arabia; School of Health Sciences, University of Petroleum and Energy Studies, Dehradun, Uttarakhand, India
Ching Siang Tan
School of Pharmacy, KPJ Healthcare University, Nilai, Malaysia; Corresponding author. School of Pharmacy, KPJ Healthcare University, 71800, Nilai, Malaysia.
Long Chiau Ming
School of Medical and Life Sciences, Sunway University, Sunway City, Malaysia
Jack Bee Chook
School of Medical and Life Sciences, Sunway University, Sunway City, Malaysia; Corresponding author.
Abdelhakim Bouyahya
Laboratory of Human Pathologies Biology, Faculty of Sciences, Mohammed V University in Rabat, Rabat, 10106, Morocco
The Food and Drug Administration (FDA) has approved vorinostat, also called Zolinza®, for its effectiveness in fighting cancer. This drug is a suberoyl-anilide hydroxamic acid belonging to the class of histone deacetylase inhibitors (HDACis). Its HDAC inhibitory potential allows it to accumulate acetylated histones. This, in turn, can restore normal gene expression in cancer cells and activate multiple signaling pathways. Experiments have proven that vorinostat induces histone acetylation and cytotoxicity in many cancer cell lines, increases the level of p21 cell cycle proteins, and enhances pro-apoptotic factors while decreasing anti-apoptotic factors. Additionally, it regulates the immune response by up-regulating programmed death-ligand 1 (PD-L1) and interferon gamma receptor 1 (IFN-γR1) expression, and can impact proteasome and/or aggresome degradation, endoplasmic reticulum function, cell cycle arrest, apoptosis, tumor microenvironment remodeling, and angiogenesis inhibition. In this study, we sought to elucidate the precise molecular mechanism by which Vorinostat inhibits HDACs. A deeper understanding of these mechanisms could improve our understanding of cancer cell abnormalities and provide new therapeutic possibilities for cancer treatment.
