title: Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells.
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 increased γH2AX 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.
authors.affiliation: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
authors.forename: Guowen
authors.initials: G
authors.lastname: Ren
authors.forename: Tongye
authors.initials: T
authors.lastname: Sha
authors.forename: Jiajie
authors.initials: J
authors.lastname: Guo
authors.forename: Wenxue
authors.initials: W
authors.lastname: Li
authors.forename: Jinjian
authors.initials: J
authors.lastname: Lu
authors.forename: Xiuping
authors.initials: X
authors.lastname: Chen
mesh_terms: D001343:Autophagy; D001688:Biological Products; D001943:Breast Neoplasms / Q000378:metabolism*; D004249:DNA Damage / Q000187:drug effects*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D010766:Phosphorylation; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014315:Triterpenes / Q000737:chemistry*
chemical_list: D001688:Biological Products; D017382:Reactive Oxygen Species; D014315:Triterpenes; C041246:cucurbitacin B