Morisaki Takashi, Katano Mitsuo
Department of Cancer Therapy and Research, Station for Collaborative Research, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Curr Med Chem. 2003 Dec;10(23):2517-21. doi: 10.2174/0929867033456431.
The cytotoxic effects of many anticancer drugs are mediated via the apoptotic pathways. Chemoresistant tumor cells have acquired the ability to evade the action of multiple classes of anti-cancer drugs. One mechanism by which tumor cells survive in the presence of chemotherapy is by increasing anti-apoptotic activities. Since mitochondria are critical 'gatekeepers' to the apoptosis process, development of cytotoxic drugs that target mitochondria may provide a new strategy to induce apoptosis in tumor cells. Mitochondrial permeability transition pore complex (PTPC) controls mitochondrial membrane permeabilization, which is a critical event in the process leading to chemotherapy-induced apoptosis. Therefore, targeting of PTPC components may overcome chemoresistance in tumor cells. Moreover, alterations in mitochondrial DNA such as mutation and the subsequent dysfunction of mitochondrial respiratory enzyme have been reported in various types of cancer, and their functional consequences are associated cancer development, chemoresistance, and therapeutic implications. In this mini-review, we aim to provide a brief review on several mitochondria-targeting strategies to overcome chemoresistance in cancer.
许多抗癌药物的细胞毒性作用是通过凋亡途径介导的。化疗耐药的肿瘤细胞已经获得了逃避多类抗癌药物作用的能力。肿瘤细胞在化疗存在的情况下存活的一种机制是增加抗凋亡活性。由于线粒体是凋亡过程的关键“守门人”，开发靶向线粒体的细胞毒性药物可能提供一种诱导肿瘤细胞凋亡的新策略。线粒体通透性转换孔复合物（PTPC）控制线粒体膜通透性，这是导致化疗诱导凋亡过程中的关键事件。因此，靶向PTPC成分可能克服肿瘤细胞的化疗耐药性。此外，在各种类型的癌症中都报道了线粒体DNA的改变，如突变以及随后线粒体呼吸酶的功能障碍，其功能后果与癌症发展、化疗耐药性及治疗意义相关。在本综述中，我们旨在简要介绍几种克服癌症化疗耐药性的线粒体靶向策略。
