Abstract Title:

Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells.

Abstract Source:

J Nat Med. 2015 Oct ;69(4):522-30. Epub 2015 May 28. PMID: 26018422

Abstract Author(s):

Guowen Ren, Tongye Sha, Jiajie Guo, Wenxue Li, Jinjian Lu, Xiuping Chen

Article Affiliation:

Guowen Ren

Abstract:

Cucurbitacin B (Cuc B), a natural compound extracted from cucurbitaceous plants, demonstrated potent anticancer activities, while the underlying mechanisms remain unclear. We investigated the anticancer effect of Cuc B on MCF-7 breast cancer cells. Cuc B drastically decreased cell viability in a concentration-dependent manner. Cuc B treatment caused DNA damage, as shown by long tails in the comet assay and increasedγH2AX protein expression. Immunofluorescence staining showed that Cuc B treatment induced nuclear γH2AX foci. Cuc B activated DNA damage pathways by phosphorylation of ATM/ATR [two large phosphatidylinositol-3-kinase-like kinase family (PIKKs) members]. Furthermore, it also induced autophagy, as evidenced by monodansylcadaverine (MDC) staining and autophagic protein expression. In addition, Cuc B treatment led to increased reactive oxygen species (ROS) formation, which was inhibited by N-acetyl-L-cysteine (NAC) pretreatment. NAC pretreatment inhibited Cuc-B-induced DNA damage and autophagy.Taken together, these results suggest that ROS-mediated Cuc-B-induced DNA damage and autophagy in MCF-7 cells, which provides new insights into the anticancer molecular mechanism of Cuc B.

Study Type : In Vitro Study

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