Identification of Mitochondria-Targeting Anticancer Compounds by an in Vitro Strategy

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• 作者：Xiang Zhang ; Shuyue Zhang ; Shaobin Zhu ; Sha Chen ; Jinyan Han ; Kaimin Gao ; Jin-zhang Zeng ; Xiaomei Yan
• 刊名：Analytical Chemistry
• 出版年：2014
• 出版时间：June 3, 2014
• 年：2014
• 卷：86
• 期：11
• 页码：5232-5237
• 全文大小：366K
• 年卷期：v.86,no.11(June 3, 2014)
• ISSN：1520-6882

文摘

Mitochondria play a pivotal role in determining the point-of-no-return of the apoptotic process. Therefore, anticancer drugs that directly target mitochondria hold great potential to evade resistance mechanisms that have developed toward conventional chemotherapeutics. In this study, we report the development of an in vitro strategy to quickly identify the therapeutic agents that induce apoptosis via directly affecting mitochondria. This result is achieved by treating isolated mitochondria with potential anticancer compounds, followed by simultaneously measuring the side scatter and mitochondrial membrane potential (螖蠄_m) fluorescence of individual mitochondria using a laboratory-built high-sensitivity flow cytometer. The feasibility of this method was tested with eight widely used anticarcinogens. Dose-dependent 螖蠄_m losses were observed for paclitaxel, antimycin A, betulinic acid, curcumin, ABT-737, and triptolide, but not for cisplatin or actinomycin D, which agrees well with their mechanisms of apoptosis induction reported in the literature. The as-developed method offers an effective approach to identify mitochondria-targeting anticancer compounds.