G226, a novel epipolythiodioxopiperazine derivative, induces autophagy and caspase-dependent apoptosis in human breast cancer cells in vitro
文献类型：期刊论文
| 作者 | He, Peng-xing1; Che, Yong-sheng2; He, Qiao-jun1; Chen, Yi3 ; Ding, Jian3
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| 刊名 | ACTA PHARMACOLOGICA SINICA
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| 出版日期 | 2014-08 |
| 卷号 | 35期号:8页码:1055-1064 |
| 关键词 | breast cancer epipolythiodioxopiperazine dideoxyverticillin apoptosis autophagy LC3 p62 caspase-8 anticancer drug |
| ISSN号 | 1671-4083 |
| DOI | 10.1038/aps.2014.47 |
| 文献子类 | Article |
| 英文摘要 | Aim: To investigate the effects of G226, a novel epipolythiodioxopiperazine derivative, on human breast cancer cells in vitro, and to explore its anticancer mechanisms. Methods: A panel of human breast cancer cell lines (MDA-MB-231, MDA-MB-468, MCF-7, ZR-75-30, BT474, BT549, SK-BR-3, T47D and HBL100) was examined. Cell proliferation was measured using sulforhodamine B assay, and cell apoptosis was detected with flow cytometry and caspase activity assay. Western blotting, immunofluorescence and targeted gene knockdowns were used to study autophagy in the cells. Results: G226 suppressed proliferation of the 9 breast cancer cell lines with a mean IC50 value of 48.5 nmoVL (the mean IC50 value of adriamycin, a reference compound, was 170.6 nmol/L). G226 induced dose-dependent apoptosis of MDA-MB-231 and MCF-7 cells, accompanied by markedly increased activities of caspase-8 and caspase-3/7, which were abolished by caspase inhibitors zVAD or zIETD. G226 also induced mitochondrial outer membrane permeabilization, resulted in the caspase-9 activation. Moreover, G226 dose-dependently enhanced the autophagy marker LC3-II and autophagy substrate p62 accumulation in the cells, which were co-localized with caspase-8. Silencing of p62 or LC3 partially diminished caspase-8 and subsequent caspase-3 activation. LC3 silencing partially reversed G226-induced apoptosis, but p62 silencing elicited a subtle effect on G226-induced apoptosis. Conclusion: The novel epipolythiodioxopiperazine derivative G226 exerts potent anticancer action against human breast cancer cells in vitro, via triggering autophagy and caspase-dependent apoptosis. |
| WOS关键词 | ANTIOXIDANT RESPONSE ELEMENT ; DEATH PATHWAYS ; PROGRAMMED NECROSIS ; STRESS-RESPONSE ; CROSS-TALK ; ACTIVATION ; INHIBITION ; P62/SQSTM1 ; MECHANISMS ; MEMBRANES |
| 资助项目 | National Natural Science Foundation of China[81321092] ; National Basic Research Program of China[2013CB932503] |
| WOS研究方向 | Chemistry ; Pharmacology & Pharmacy |
| 语种 | 英语 |
| CSCD记录号 | CSCD:5206240 |
| WOS记录号 | WOS:000340510400008 |
| 出版者 | ACTA PHARMACOLOGICA SINICA |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/276959]  |
| 专题 | 药理学第一研究室 中科院受体结构与功能重点实验室 新药研究国家重点实验室 |
| 通讯作者 | Chen, Yi |
| 作者单位 | 1.Zhejiang Univ, Sch Pharmaceut Sci, Inst Pharmacol & Toxicol, Hangzhou 310058, Zhejiang, Peoples R China; 2.Beijing Inst Pharmacol & Toxicol, Beijing 100190, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Div Antitumor Pharmacol, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | He, Peng-xing,Che, Yong-sheng,He, Qiao-jun,et al. G226, a novel epipolythiodioxopiperazine derivative, induces autophagy and caspase-dependent apoptosis in human breast cancer cells in vitro[J]. ACTA PHARMACOLOGICA SINICA,2014,35(8):1055-1064. |
| APA | He, Peng-xing,Che, Yong-sheng,He, Qiao-jun,Chen, Yi,&Ding, Jian.(2014).G226, a novel epipolythiodioxopiperazine derivative, induces autophagy and caspase-dependent apoptosis in human breast cancer cells in vitro.ACTA PHARMACOLOGICA SINICA,35(8),1055-1064. |
| MLA | He, Peng-xing,et al."G226, a novel epipolythiodioxopiperazine derivative, induces autophagy and caspase-dependent apoptosis in human breast cancer cells in vitro".ACTA PHARMACOLOGICA SINICA 35.8(2014):1055-1064. |
入库方式： OAI收割
来源：上海药物研究所
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