Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
School of Pharmacy, China Medical University, Taichung, Taiwan.
Food Chem Toxicol. 2014 Mar;65:205-12. doi: 10.1016/j.fct.2013.12.026. Epub 2013 Dec 25.
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.
4β-羟基羽扇豆烷醇 E 是从秘鲁酸浆中提取的一种具有生物活性的羽扇豆烷醇。4β-羟基羽扇豆烷醇 E 可引起人乳腺癌 MCF-7 细胞中活性氧的产生和细胞凋亡。我们进一步发现，4β-羟基羽扇豆烷醇 E 诱导 DNA 损伤，并调节 MCF-7 细胞中的 DNA 损伤信号。DNA 损伤传感器和修复蛋白通过 4β-羟基羽扇豆烷醇 E 迅速清除 DNA 损伤。共济失调毛细血管扩张突变蛋白（ATM）依赖性 DNA 损伤信号通路参与了 4β-羟基羽扇豆烷醇 E 诱导的 MCF-7 细胞凋亡。非同源末端连接途径，而不是同源重组，是 MCF-7 细胞对 4β-羟基羽扇豆烷醇 E 诱导的 DNA 损伤的主要保护途径。4β-羟基羽扇豆烷醇 E 对碱基切除修复途径没有显著影响。在本研究中，我们将 4β-羟基羽扇豆烷醇 E 诱导的 DNA 损伤作为研究工具，用于研究乳腺癌细胞中的 DNA 修复信号。我们还建议 4β-羟基羽扇豆烷醇 E 在致癌进展中发挥其抗肿瘤活性，并发展成为一种饮食化学预防剂。
