Mitochondria-targeting therapeutic strategies for overcoming chemoresistance and progression of cancer.
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.
Morisaki
Takashi
T
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. 9h7m@surg1.med.kyushu-u.ac.jp
Katano
Mitsuo
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002463:Cell Membrane Permeability / Q000187:drug effects / Q000502:physiology; D004272:DNA, Mitochondrial / Q000235:genetics; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000494:pharmacology
D004272:DNA, Mitochondrial; D019253:Proto-Oncogene Proteins c-bcl-2