title: Non-homologous end joining pathway is the major route of protection against 4β-hydroxywithanolide E-induced DNA damage in MCF-7 cells.
abstract: 4β-Hydroxywithanolide E is a bioactive withanolide extracted from Physalis peruviana. 4β-Hydroxywithanolide E caused reactive oxygen species production and cell apoptosis in human breast cancer MCF-7 cells. We further found that 4β-hydroxywithanolide E induced DNA damage and regulated the DNA damage signaling in MCF-7 cells. The DNA damage sensors and repair proteins act promptly to remove DNA lesions by 4β-hydroxywithanolide E. The ataxia-telangiectasia mutated protein (ATM)-dependent DNA damage signaling pathway is involved in 4β-hydroxywithanolide E-induced apoptosis of MCF-7 cells. Non-homologous end joining pathway, but not homologous recombination, is the major route of protection of MCF-7 cells against 4β-hydroxywithanolide E-induced DNA damage. 4β-Hydroxywithanolide E had no significant impact on the base excision repair pathway. In this study, we examined the 4β-hydroxywithanolide E-induced DNA damage as a research tool in project investigating the DNA repair signaling in breast cancer cells. We also suggest that 4β-hydroxywithanolide E assert its anti-tumor activity in carcinogenic progression and develop into a dietary chemopreventive agent.
authors.affiliation: Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
authors.forename: B-J
authors.initials: BJ
authors.lastname: You
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Y-C
authors.initials: YC
authors.lastname: Wu
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: C-L
authors.initials: CL
authors.lastname: Lee
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan. Electronic address: hong@mail.cmu.edu.tw.
authors.forename: H-Z
authors.initials: HZ
authors.lastname: Lee
mesh_terms: D004249:DNA Damage; D059766:DNA End-Joining Repair; D006801:Humans; D061986:MCF-7 Cells; D054358:Withanolides / Q000633:toxicity*
chemical_list: C554450:4-hydroxywithanolide E; D054358:Withanolides
keywords: 4β-Hydroxywithanolide E; ATM-dependent DNA damage; Breast cancer; Dietary chemopreventive agent; Non-homologous end joining pathway; Reactive oxygen species