Kaur Ishnoor, Behl Tapan, Sachdeva Monika, Bungau Simona, Venkatachalam Thangavel
Chitkara College of Pharmacy, Chitkara University, Punjab,India.
Fatima College of Health Sciences, Al Ain,United Arab Emirates.
Curr Mol Pharmacol. 2021;14(6):1066-1082. doi: 10.2174/1874467214666210120145537.
The role of mitochondria in the apoptosis signaling cell death pathway is regulated by extrinsic and intrinsic pathway, encompassing multiple components like the Bcl-2 family of proteins, death receptors, caspases, Smac/DIABLO, IAPs, Omi/HtrA2 and cytochrome c. These entities serve as effective molecular targets for numerous drugs targeting mitochondrial apoptotic pathways, mainly emphasizing oncology therapeutics. Defective apoptosis is an acquired hallmark of cancer cells, which promotes the establishment of apoptosis-targeting anti-cancer drugs in cancer treatment. The review provides an overview of the Bcl-2 inhibiting, IAPs antagonizing, caspase inhibiting and BH3 mimicking actions, mediated by anti-cancer drugs, rendering beneficial outcomes in different forms of cancer. The authors elaborate on the significance of synthetic and natural agents, targeting the mitochondrial apoptotic pathway, in ameliorating tumor cell growth in the body, and the specificity and effectiveness of these agents, motivating the researchers to explore mitochondrial apoptosis targeting of anti-tumor drugs of both herbal and synthetic origin. Thus, the review aims to predict this dynamic approach in oncology, simultaneously highlighting the challenges and future prospects, providing an opportunity to the experts to "go over with a fine tooth comb" in understanding this "programmed cell death pathway", and establishing reliability and accuracy of this therapeutic paradigm in the upcoming future.
线粒体在凋亡信号传导细胞死亡途径中的作用受外在和内在途径调控,涉及多种成分,如Bcl-2蛋白家族、死亡受体、半胱天冬酶、Smac/DIABLO、IAPs、Omi/HtrA2和细胞色素c。这些实体是众多靶向线粒体凋亡途径药物的有效分子靶点,主要侧重于肿瘤治疗。凋亡缺陷是癌细胞的一个后天特征,这促进了在癌症治疗中建立靶向凋亡的抗癌药物。本综述概述了抗癌药物介导的Bcl-2抑制、IAPs拮抗、半胱天冬酶抑制和BH3模拟作用,在不同形式的癌症中产生了有益的结果。作者阐述了靶向线粒体凋亡途径的合成和天然药物在改善体内肿瘤细胞生长方面的意义,以及这些药物的特异性和有效性,激励研究人员探索源自草药和合成药物的抗肿瘤药物对线粒体凋亡的靶向作用。因此,本综述旨在预测肿瘤学中的这种动态方法,同时突出挑战和未来前景,为专家提供一个“仔细梳理”的机会,以理解这种“程序性细胞死亡途径”,并在未来确立这种治疗模式的可靠性和准确性。