期刊
ONCOLOGY REPORTS
卷 33, 期 6, 页码 2711-2718出版社
SPANDIDOS PUBL LTD
DOI: 10.3892/or.2015.3915
关键词
mitochondrial membrane potential; reactive oxygen species; silibinin; autophagy; ATP; BNIP3
类别
资金
- Zhejiang Provincial Natural Science Foundation of China [LQ14H290002, LY12H29010]
- Zhejiang Provincial Administration of Traditional Chinese Medicine [2014ZB012]
- Zhejiang Provincial Natural Science Foundation of China [LQ14H290002, LY12H29010]
- Zhejiang Provincial Administration of Traditional Chinese Medicine [2014ZB012]
Silibinin, derived from the milk thistle plant (Silybum marianum), has anticancer and chemopreventive properties. Silibinin has been reported to inhibit the growth of various types of cancer cells. However, the mechanisms by which silibinin exerts an anticancer effect are poorly defined. The present study aimed to investigate whether silibinin-induced cell death might be attributed to autophagy and the underlying mechanisms in human MCF7 breast cancer cells. Our results showed that silibinin-induced cell death was greatly abrogated by two specific autophagy inhibitors, 3-methyladenine (3-MA) and bafilomycin-A1 (Baf-A1). In addition, silibinin triggered the conversion of light chain 3 (LC3)-I to LC3-II, promoted the upregulation of Atg12-Atg5 formation, increased Beclin-1 expression, and decreased the Bcl-2 level. Moreover, we noted elevated reactive oxygen species (ROS) generation, concomitant with the dissipation of mitochondrial transmembrane potential (Delta Psi m) and a drastic decline in ATP levels following silibinin treatment, which were effectively prevented by the antioxidants, N-acetylcysteine and ascorbic acid. Silibinin stimulated the expression of Bcl-2 adenovirus ElB 19-kDa-interacting protein 3 (BNIP3), a pro-death Bcl-2 family member, and silencing of BNIP3 greatly inhibited silibinin-induced cell death, decreased ROS production, and sustained AI FM and ATP levels. Taken together, these findings revealed that silibinin induced autophagic cell death through ROS-dependent mitochondrial dysfunction and ATP depletion involving BNIP3 in MCF7 cells.
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