恢复线粒体功能作为癌症治疗的一个靶点。
Restoration of mitochondria function as a target for cancer therapy.
作者信息
Bhat Tariq A, Kumar Sandeep, Chaudhary Ajay K, Yadav Neelu, Chandra Dhyan
机构信息
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA.
出版信息
Drug Discov Today. 2015 May;20(5):635-43. doi: 10.1016/j.drudis.2015.03.001. Epub 2015 Mar 9.
Abstract
Defective oxidative phosphorylation has a crucial role in the attenuation of mitochondrial function, which confers therapy resistance in cancer. Various factors, including endogenous heat shock proteins (HSPs) and exogenous agents such as dichloroacetate, restore respiratory and other physiological functions of mitochondria in cancer cells. Functional mitochondria might ultimately lead to the restoration of apoptosis in cancer cells that are refractory to current anticancer agents. Here, we summarize the key reasons contributing to mitochondria dysfunction in cancer cells and how restoration of mitochondrial function could be exploited for cancer therapeutics.
摘要
氧化磷酸化缺陷在线粒体功能衰减中起关键作用，而线粒体功能衰减赋予癌症治疗抗性。包括内源性热休克蛋白（HSPs）以及二氯乙酸等外源性物质在内的多种因素，可恢复癌细胞中线粒体的呼吸及其他生理功能。功能性线粒体最终可能促使对当前抗癌药物难治的癌细胞恢复凋亡。在此，我们总结了导致癌细胞线粒体功能障碍的关键原因，以及如何利用线粒体功能的恢复来进行癌症治疗。
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Sci Rep. 2015 Jan 14;5:7762. doi: 10.1038/srep07762.
2
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3
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