Compound 13, an α1-selective small molecule activator of AMPK, potently inhibits melanoma cell proliferation

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• 作者：Xueqing Hu ; Fangzhen Jiang ; Qi Bao ; Huan Qian ; Quan Fang ; Zheren Shao
• 刊名：Tumor Biology
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：37
• 期：1
• 页码：1071-1078
• 全文大小：740 KB
• 刊物主题：Cancer Research;
• 出版者：Springer Netherlands
• ISSN：1423-0380
• 卷排序：37

文摘

It is vital to develop new therapeutic agents for the treatment of melanoma. In the current study, we studied the potential effect of Compound 13 (C13), a novel α1-selective AMP-activated protein kinase (AMPK) activator, in melanoma cells. We showed that C13 exerted mainly cytostatic, but not cytotoxic activities in melanoma cells. C13 potently inhibited proliferation in melanoma cell lines (A375, OCM-1 and B16), but not in B10BR melanocytes. Meanwhile, the AMPK activator inhibited melanoma cell cycle progression by inducing G1-S arrest. Significantly, we failed to detect significant melanoma cell death or apoptosis after the C13 treatment. For the mechanism study, we showed that C13 activated AMPK and inhibited mammalian target of rapamycin complex 1 (mTORC1) signaling in melanoma cells through interaction with the α1 subunit. Short hairpin RNA (shRNA)-mediated knockdown of AMPKα1 not only blocked C13-mediated AMPK activation but also abolished its antiproliferative activity against melanoma cells. Together, these results show that C13 inhibits melanoma cell proliferation through activating AMPK signaling. Our data suggest that C13 along with other small molecular AMPK activators may be beneficial for patients with melanoma.KeywordsMelanomaAMPKCompound 13mTORC1 and proliferation