Mollugin induces tumor cell apoptosis and autophagy via the PI3K/AKT/mTOR/p70S6K and ERK signaling pathways

被引:69
|
作者
Zhang, Li [1 ]
Wang, Handong [1 ]
Zhu, Jianhong [1 ]
Xu, Jianguo [1 ]
Ding, Ke [1 ]
机构
[1] Nanjing Univ, Sch Med, Jinling Hosp, Dept Neurosurg, Nanjing 210008, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
Mollugin; Apoptosis; Autophagy; PI3K/AKT/mTOR/p7036K; ERK; FTY720; INDUCTION; BETA;
D O I
10.1016/j.bbrc.2014.05.101
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mollugin, a bioactive phytochemical isolated from Rubia cordifolia L, has shown preclinical anticancer efficacy in various cancer models. However the effects of mollugin in regulating cancer cell survival and death remains undefined. In the present study we found that mollugin exhibited cytotoxicity on various cancer models. The suppression of cell viability was due to the induction of mitochondria apoptosis. In addition, the presence of autophagic hallmarks was observed in mollugin-treated cells. Notably, blockade of autophagy by a chemical inhibitor or RNA interference enhanced the cytotoxicity of mollugin. Further experiments demonstrated that phosphatidylinositide 3-kinases/protein kinase B/mammalian target of rapamycin/p70S6 kinase (PI3K/AKT/mTOR/p70S6K) and extracellular regulated protein kinases (ERK) signaling pathways participated in mollugin-induced autophagy and apoptosis. Together, these findings support further studies of mollugin as candidate for treatment of human cancer cells. (C) 2014 Elsevier Inc. All rights reserved.
引用
收藏
页码:247 / 254
页数:8
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