Galangin suppresses HepG2 cell proliferation by activating the TGF-β receptor/Smad pathway

被引：41
|
作者：
Wang, Yajun [1 ,2 ]
Wu, Jun [2 ]
Lin, Biyun [1 ]
Li, Xv [1 ]
Zhang, Haitao [1 ]
Ding, Hang [1 ]
Chen, Xiaoyi [1 ]
Lan, Liubo [1 ]
Luo, Hui [3 ]
机构：
[1] Guangdong Med Coll, Dept Biochem & Mol Biol, Dongguan 523808, Guangdong, Peoples R China
[2] Guangdong Med Coll, Affiliated Hosp, Zhanjiang 524001, Guangdong, Peoples R China
[3] Guangdong Med Coll, Dept Chem, Zhanjiang 524023, Guangdong, Peoples R China
来源：
TOXICOLOGY | 2014年 / 326卷
基金：
中国国家自然科学基金;
关键词：
Galangin; Autophagy; Smad; TGF-beta receptor; Autophagy-related gene; HEPATOCELLULAR-CARCINOMA CELLS; ENDOPLASMIC-RETICULUM STRESS; PROTEIN CONJUGATION SYSTEM; CANCER-CELLS; INHIBITS PROLIFERATION; TUMOR-SUPPRESSOR; UP-REGULATION; BECLIN; AUTOPHAGY; APOPTOSIS;
D O I：
10.1016/j.tox.2014.09.010
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
Galangin can suppress hepatocellular carcinoma (HCC) cell proliferation. In this study, we demonstrated that galangin induced autophagy by activating the transforming growth factor (TGF)-beta receptor/Smad pathway and increased TGF-beta receptor I (RI), TGF-beta RII, Smad1, Smad2, Smad3 and Smad4 levels but decreased Smad6 and Smad7 levels. Autophagy induced by galangin appears to depend on the TGF-beta receptor/Smad signalling pathway because the down-regulation of Smad4 by siRNA or inhibition of TGF-beta receptor activation by LY2109761 blocked galangin-induced autophagy. The down-regulation of Beclin1, autophagy-related gene (ATG) 16L, ATG12 and ATG3 restored HepG2 cell proliferation and prevented galangin-induced apoptosis. Our findings indicate a novel mechanism for galangin-induced autophagy via activation of the TGF-beta receptor/Smad pathway. The induction of autophagy thus reflects the anti-proliferation effect of galangin on HCC cells. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码：9 / 17
页数：9
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