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Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells
Ren G.2; Sha T.1; Guo J.2; Li W.2; Lu J.2; Chen X.2
2015-10-11
Source PublicationJournal of Natural Medicines
ISSN18610293 13403443
Volume69Issue:4Pages:522-530
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 γHAX protein expression. Immunofluorescence staining showed that Cuc B treatment induced nuclear γHAX 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.

KeywordAutophagy Breast Cancer Cucurbitacin b Dna Damage Ros
DOI10.1007/s11418-015-0918-4
URLView the original
Indexed BySCI
WOS Research AreaPharmacology & Pharmacy
WOS SubjectChemistry, Medicinal ; Pharmacology & Pharmacy
WOS IDWOS:000360852400009
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Cited Times [WOS]:23   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Affiliation1.Rizhao Hospital of TCM
2.Universidade de Macau
Recommended Citation
GB/T 7714
Ren G.,Sha T.,Guo J.,et al. Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells[J]. Journal of Natural Medicines,2015,69(4):522-530.
APA Ren G.,Sha T.,Guo J.,Li W.,Lu J.,&Chen X..(2015).Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells.Journal of Natural Medicines,69(4),522-530.
MLA Ren G.,et al."Cucurbitacin B induces DNA damage and autophagy mediated by reactive oxygen species (ROS) in MCF-7 breast cancer cells".Journal of Natural Medicines 69.4(2015):522-530.
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