Drugs targeting mitochondrial functions to control tumor cell growth
Drugs targeting mitochondrial functions to control tumor cell growth
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DOI：
10.1016/j.bcp.2005.03.021
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发表时间：
2005-07-01
影响因子：
5.8
通讯作者：
Bailly, C
中科院分区：
文献类型：
--
作者：
Dias, N;Bailly, C
线粒体是细胞的动力室，位于许多细胞通路的十字路口。它们在能量代谢中发挥核心作用，调节钙通量并参与细胞凋亡。线粒体功能障碍与各种病理生理疾病有关，特别是神经退行性疾病和癌症。结构多样的药物制剂已显示出对线粒体超微结构和功能的直接影响，无论是在 DNA 水平上还是在靶向位于线粒体内膜或外膜的蛋白质上。简要回顾了作用于特定线粒体位点的化学多样化小分子的分子靶点和作用机制，例如呼吸链、DNA 生物发生、钾通道、Bcl-2 蛋白和渗透性转换孔 (PTP)。专门损害线粒体结构和功能完整性的药物可能会提供对抗癌细胞增殖的新机会，前提是这些分子可以选择性地递送到肿瘤部位。这里报道的不同例子表明，线粒体损伤或衰竭可以迅速导致细胞存活和增殖的抑制。线粒体损伤可能是一种成功的抗癌策略。 (c) 2005 Elsevier Inc. 保留所有权利。
Mitochondria, the power houses of the cell, are at the cross-road of many cellular pathways. They play a central role in energy metabolism, regulate calcium flux and are implicated in apoptosis. Mitochondrial dysfunctions have been associated with various physiopathological disorders, especially neurodegenerative diseases and cancer. Structurally diverse pharmacological agents have shown direct effects on mitochondria ultra-structures and functions, either at the DNA level or upon targeting proteins located in the inner or outer mitochondrial membranes. The brief review deals with the molecular targets and mechanisms of action of chemically diverse small molecules acting on specific mitochondrial loci, such as the respiratory chain, DNA biogenesis, potassium channels, the Bcl-2 protein and the permeability transition pores (PTP). Drugs, which specifically compromise the structural and functional integrity of mitochondria, may provide novel opportunities to combat cancer cell proliferation, providing that these molecules can be selectively delivered to tumor sites. Different examples reported here show that mitochondrial insult or failure can rapidly lead to inhibition of cell survival and proliferation. Mitochondrial impairment may be a successful anti-cancer strategy. (c) 2005 Elsevier Inc. All rights reserved.