Conditioned medium from actinomycin D-treated apoptotic cells induces mitochondria-dependent apoptosis in bystander cells

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• 作者：Cuihong Jin^a ; Shengwen Wu^a ; Xiaobo Lu^a ; Qiufang Liu^a ; Lifeng Zhang^a ; Jinghua Yang^a ; Qi Xi^b ; Yuan Cai^a ; ^{cmuycai@163.com}
• 关键词：Chemical-induced bystander effect ; ACTD-treated conditioned medium ; Medium transfer ; Mitochondria-dependent apoptosis
• 刊名：Toxicology Letters
• 出版年：2012
• 期刊代码：49_03784274
• 类别：pha
• 出版时间：20 May, 2012
• 卷：211
• 期：1
• 页码：45-53
• 文件大小：1404 K

摘要

Chemical-induced bystander effects have been known for several years, but the underlying mechanism is still seldom investigated. Previous researchers have found that mitomycin C and phleomycin induced micronuclei in bystander cells the same as in exposed cells. We previously demonstrated the ability of actinomycin D (ACTD) to induce bystander effects in normal Chinese hamster fibroblast V79 cells and found that conditioned medium (CM) obtained from ACTD-exposed apoptotic cells induced apoptosis in bystander cells. The present study further explores the probable mechanism of apoptosis in bystander cells. The main findings of this study are: (1) ACTD-treated CM induced apoptosis in bystander cells in a time-dependent manner, which was confirmed with morphological changes. (2) ACTD-treated CM increased the mRNA and protein levels of pro-apoptotic p53 and Bax, whereas it decreased those of anti-apoptotic Bcl-2 in bystander cells; these were all time-dependent effects. Reactive oxygen species (ROS) were also involved in apoptosis of bystander cells. (3) ACTD-treated CM reduced mitochondria membrane potential and induced cytochrome c release. (4) ACTD-treated CM induced G1 cell phase arrest, which may be another response in bystander cells when cultured with CM. These results suggest that chemical-treated CM induces p53-Bcl-2/Bax-cytochrome c signaling (i.e., mitochondria pathway)-dependent apoptosis in bystander cells, which is a kinetic response.