Taraxacum mongolicum extract induced endoplasmic reticulum stress associated-apoptosis in triple-negative breast cancer cells

蒲公英 切碎 细胞凋亡 活力测定 未折叠蛋白反应 生物 MTT法 内质网 癌症研究 分子生物学 医学 细胞生物学 生物化学 病理 中医药 替代医学
作者
Xiaohong Li,Xi-Ran He,Yanyan Zhou,Hai-Yu Zhao,Wenxian Zheng,Shan-Tong Jiang,Qun Zhou,Pingping Li,Shu-Yan Han
出处
期刊:Journal of Ethnopharmacology [Elsevier]
卷期号:206: 55-64 被引量:24
标识
DOI:10.1016/j.jep.2017.04.025
摘要

Triple-negative breast cancer (TNBC) is an aggressive and deadly breast cancer subtype with limited treatment options. It is necessary to seek complementary strategies for TNBC management. Taraxacum mongolicum, commonly named as dandelion, is a herb medicine with anti-cancer activity and has been utilized to treat mammary abscess, hyperplasia of mammary glands from ancient time in China, but the scientific evidence and action mechanisms still need to be studied.This study was intended to investigate the therapeutic effect and molecular mechanisms of dandelion extract in TNBC cell line.Dandelion extract was prepared and purified, and then its chemical composition was determined. Cell viability was evaluated by MTT assay. Analysis of cell apoptosis and cell cycle was assessed by flow cytometry. The expression levels of mRNA and proteins were determined by real-time PCR and Western blotting, respectively. Caspase inhibitor Z-VAD-FMK and CHOP siRNA were used to confirm the cell apoptosis induced by dandelion extract.Dandelion extract significantly decreased MDA-MB-231cell viability, triggered G2/M phase arrest and cell apoptosis. Concurrently, it caused a markedly increase of cleaved caspase-3 and PARP proteins. Caspase inhibitor Z-VAD-FMK abolished the apoptosis triggered by dandelion extract. The three ER stress-related signals were strongly induced after dandelion treatment, including increased mRNA expressions of ATF4, ATF6, XBP1s, GRP78 and CHOP genes, elevated protein levels of phosphorylated PERK, eIF-2α, IRE1, as well as the downstream molecules of CHOP and GRP78. MDA-MB-231 cells transfected with CHOP siRNA significantly reduced apoptosis induced by dandelion extract. The underlying mechanisms at least partially ascribe to the strong activation of PERK/p-eIF2α/ATF4/CHOP axis.ER stress related cell apoptosis accounted for the anti-cancer effect of dandelion extract, and these findings support dandelion extract might be a potential therapeutic approach to treat TNBC.
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