Ursolic acid-induced AMP-activated protein kinase (AMPK) activation contributes to growth inhibition and apoptosis in human bladder cancer T24 cells

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• 作者：Qing-you Zheng^a ; ^{qingyouzheng@yahoo.com} ; Feng-suo Jin^b ; Chen Yao^c ; Tong Zhang^a ; Guo-hui Zhang^a ; Xing Ai^a
• 关键词：AMPK ; AMP-activated protein kinase ; ACC ; acetyl-CoA carboxylase ; AICAR ; 5-aminoimidazole-4-carboxamide-1-尾-d-ribofuranoside ; FACS ; fluorescence-activated cell sorting ; JNK ; c-Jun N-terminal kinase ; mTORC1 ; mTOR complex 1 ; S6K1 ; ribosomal p70 S6 kinase ; T
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：23 March, 2012
• 卷：419
• 期：4
• 页码：741-747
• 文件大小：549 K

摘要

Ursolic acid (UA) has shown the anti-tumor properties against a number of human cancers both in vivo and in vitro, however, its effect in bladder cancer and the corresponding mechanisms of action remain largely unknown. Here we found that UA dose-dependently induced growth inhibition and apoptosis in human bladder cancer T24 cells, and activation of AMP-activated protein kinase (AMPK) may contribute to the process. Our Western-blot results demonstrated a significant AMPK activation after UA treatment in T24 cells. Notably, knockdown of AMPK伪 by the targeted shRNA largely inhibited UA-induced T24 cell growth inhibition and apoptosis, while an AMPK activator 5-aminoimidazole-4-carboxamide-1-尾-d-ribofuranoside (AICAR) or a constitutively active form of AMPK mimic UA鈥檚 effect. We found the ceramide level was increased after UA treatment in T24 cells, and UA-induced AMPK activation and T24 cell apoptosis were inhibited by ceramide synthase inhibitor fumonisin B1, and was enhanced by exogenously adding cell permeable short-chain ceramide (C6), suggesting that ceramide might serve as an upstream signal for AMPK activation. Further, activation of AMPK by UA promoted c-Jun N-terminal kinase (JNK) activation, but inhibited mTOR complex 1 (mTORC1) signaling to cause survivin down-regulation. Our study suggests that activation of AMPK by UA contributes to growth inhibition and apoptosis in human bladder cancer cells.