RETRACTED: Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation (Retracted Article)

被引:110
作者
Guan, Feng [1 ]
Ding, Youming [2 ]
Zhang, Yemin [1 ]
Zhou, Yu [2 ]
Li, Mingxin [1 ]
Wang, Changhua [1 ]
机构
[1] Wuhan Univ, Sch Basic Med Sci, Dept Pathophysiol, Wuhan 430071, Peoples R China
[2] Wuhan Univ, Renmin Hosp, Dept Hepatobiliary & Laparascop Surg, Wuhan 430060, Peoples R China
基金
中国国家自然科学基金;
关键词
UBIQUITIN-PROTEASOME SYSTEM; PI3K/AKT SIGNALING PATHWAY; INHIBITOR MK-2206; APOPTOSIS; AMPK; INVASION; ACTIVATION; INDUCTION; PROTEIN; GROWTH;
D O I
10.1371/journal.pone.0146553
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Previous studies have evidenced that the anticancer potential of curcumin (diferuloylmethane), a main yellow bioactive compound from plant turmeric was mediated by interfering with PI3K/Akt signaling. However, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that curcumin treatment reduced Akt protein expression in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells, along with an activation of autophagy and suppression of ubiquitin-proteasome system (UPS) function. The curcumin-reduced Akt expression, cell proliferation, and migration were prevented by genetic and pharmacological inhibition of autophagy but not by UPS inhibition. Additionally, inactivation of AMPK by its specific inhibitor compound C or by target shRNA-mediated silencing attenuated curcumin-activated autophagy. Thus, these results indicate that curcumin-stimulated AMPK activity induces activation of the autophagy-lysosomal protein degradation pathway leading to Akt degradation and the subsequent suppression of proliferation and migration in breast cancer cell.
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页数:18
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