Yadav Neelu, Chandra Dhyan
Department of Pharmacology Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, United States.
Department of Pharmacology Therapeutics, Roswell Park Cancer Institute, Buffalo, NY, United States.
Mitochondrion. 2014 May;16:18-25. doi: 10.1016/j.mito.2013.11.005. Epub 2013 Dec 10.
Cancer cells are resistant to conventional chemotherapy and radiotherapy, however, the molecular mechanisms of resistance to therapy remain unclear. Cellular survival machinery protects mitochondrial integrity against endogenous or exogenous stresses. Prodeath molecules orchestrate around mitochondria to initiate and execute cell death in cancer, and also play an underappreciated role in survival of cancer cells. Prosurvival mechanisms can operate at mitochondrial and postmitochondrial levels to attenuate core apoptotic death program. It is intriguing to explore how prosurvival and prodeath molecules crosstalk to regulate mitochondrial functions leading to increased cancer cell survival. This review describes some putative survival mechanisms at mitochondria, which may play a role in designing effective agents for cancer prevention and therapy. These survival pathways may also have significance in understanding other human pathophysiological conditions including diabetes, cardiovascular, autoimmune, and neurodegenerative diseases.
癌细胞对传统化疗和放疗具有抗性,然而,治疗抗性的分子机制仍不清楚。细胞存活机制可保护线粒体完整性免受内源性或外源性应激影响。促凋亡分子围绕线粒体发挥作用,在癌症中启动并执行细胞死亡,同时在癌细胞存活中也发挥着未被充分认识的作用。促存活机制可在线粒体及线粒体后水平发挥作用,以减弱核心凋亡死亡程序。探究促存活分子和促凋亡分子如何相互作用以调节线粒体功能从而导致癌细胞存活率增加,这很有意思。本综述描述了线粒体的一些假定存活机制,这些机制可能在设计有效的癌症预防和治疗药物中发挥作用。这些存活途径在理解包括糖尿病、心血管疾病、自身免疫性疾病和神经退行性疾病在内的其他人类病理生理状况方面可能也具有重要意义。