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汉防己甲素通过调控 MAPK-mTOR 通路诱导 MDA-MB-231 细胞自噬。

Wogonoside induces autophagy in MDA-MB-231 cells by regulating MAPK-mTOR pathway.

机构信息

State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China.

出版信息

Food Chem Toxicol. 2013 Jan;51:53-60. doi: 10.1016/j.fct.2012.09.012. Epub 2012 Sep 18.

DOI:10.1016/j.fct.2012.09.012
PMID:23000445
Abstract

Previous studies have demonstrated that wogonoside, a bioactive flavonoid extracted from the root of Scutellaria baicalensis Gerogi, has anti-inflammatory and anti-angiogenic activities. In this study, we evaluated wogonoside-induced autophagy on human breast MDA-MB-231 cells. We report that wogonoside triggered the formation of microtubule-associated protein-light chain 3 (MAP-LC3) positive autophagosomes and the accumulation of acidic vesicular and autolysosomes in MDA-MB-231 cells. In addition, cells treated by wogonoside developed autophagosome-like characteristics, including single and double membrane vacuoles containing intact and degraded cellular debris. The results showed that wogonoside promotes the expression of LC3-II and Beclin-1. Furthermore, wogonoside inhibited cell growth of MDA-MB-231 cells in a concentration- and time-dependent manner, which was associated with wogonoside-induced autophagy. Wogonoside also suppressed the activation of mammalian target of rapamycin (mTOR) and p70-S6 kinase (p70S6K) by regulating the expression of the extracellular signal-regulated kinase (ERK1/2) and p38 involved mitogen-activated protein kinase (MAPK) signaling pathway. Taken together, these results suggest that wogonoside partially inhibits MDA-MB-231 cell growth by inducing autophagy through the MAPK-mTOR pathway and may be a promising anti-tumor agent.

摘要

先前的研究表明,从黄芩根中提取的生物活性黄酮类化合物黄芩苷具有抗炎和抗血管生成作用。在这项研究中,我们评估了黄芩苷对人乳腺癌 MDA-MB-231 细胞自噬的诱导作用。我们报告称,黄芩苷触发了微管相关蛋白轻链 3(MAP-LC3)阳性自噬体的形成和 MDA-MB-231 细胞中酸性囊泡和自噬溶酶体的积累。此外,用黄芩苷处理的细胞表现出自噬体样特征,包括含有完整和降解细胞碎片的单膜和双膜空泡。结果表明,黄芩苷促进 LC3-II 和 Beclin-1 的表达。此外,黄芩苷以浓度和时间依赖的方式抑制 MDA-MB-231 细胞的生长,这与黄芩苷诱导的自噬有关。黄芩苷还通过调节细胞外信号调节激酶(ERK1/2)和丝裂原激活蛋白激酶(MAPK)信号通路中涉及的 p38 来抑制哺乳动物雷帕霉素靶蛋白(mTOR)和 p70-S6 激酶(p70S6K)的激活。总之,这些结果表明,黄芩苷通过 MAPK-mTOR 通路诱导自噬,部分抑制 MDA-MB-231 细胞的生长,可能是一种有前途的抗肿瘤药物。

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