El Omari Nasreddine, Khalid Asaad, Makeen Hafiz A, Alhazmi Hassan A, Albratty Mohammed, Mohan Syam, Tan Ching Siang, Ming Long Chiau, Chook Jack Bee, Bouyahya Abdelhakim
High Institute of Nursing Professions and Health Techniques of Tetouan, Tetouan, Morocco.
Substance Abuse and Toxicology Research Center, Jazan University, P.O. Box 114, Postal Code 45142, Jazan, Saudi Arabia.
Heliyon. 2024 Jun 18;10(12):e33052. doi: 10.1016/j.heliyon.2024.e33052. eCollection 2024 Jun 30.
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.
美国食品药品监督管理局（FDA）已批准伏立诺他（也称为Zolinza®）用于抗癌，因其具有抗癌功效。这种药物是一种辛二酰苯胺异羟肟酸，属于组蛋白去乙酰化酶抑制剂（HDACis）类别。其HDAC抑制潜能使其能够积累乙酰化组蛋白。反过来，这可以恢复癌细胞中的正常基因表达并激活多种信号通路。实验证明，伏立诺他在许多癌细胞系中诱导组蛋白乙酰化和细胞毒性，增加p21细胞周期蛋白水平，增强促凋亡因子同时降低抗凋亡因子。此外，它通过上调程序性死亡配体1（PD-L1）和干扰素γ受体1（IFN-γR1）的表达来调节免疫反应，并且可以影响蛋白酶体和/或聚集体降解、内质网功能、细胞周期停滞、凋亡、肿瘤微环境重塑和血管生成抑制。在本研究中，我们试图阐明伏立诺他抑制HDACs的精确分子机制。对这些机制的更深入理解可以增进我们对癌细胞异常的认识，并为癌症治疗提供新的治疗可能性。
