Compound 13, an α1-selective small molecule activator of AMPK, potently inhibits melanoma cell proliferation.
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.
Department of Plastic Surgery, The Second Affiliated Hospital, Medical School, Zhejiang University, 88 Jie Fang Road, Hangzhou, 310009, China.
Xueqing
X
Hu
Department of Plastic Surgery, The Second Affiliated Hospital, Medical School, Zhejiang University, 88 Jie Fang Road, Hangzhou, 310009, China.
Fangzhen
F
Jiang
Department of Plastic Surgery, The Second Affiliated Hospital, Medical School, Zhejiang University, 88 Jie Fang Road, Hangzhou, 310009, China.
Qi
Q
Bao
Department of Plastic Surgery, The Second Affiliated Hospital, Medical School, Zhejiang University, 88 Jie Fang Road, Hangzhou, 310009, China.
Huan
H
Qian
Department of Plastic Surgery, The Second Affiliated Hospital, Medical School, Zhejiang University, 88 Jie Fang Road, Hangzhou, 310009, China.
Quan
Q
Fang
Department of Plastic Surgery, The Second Affiliated Hospital, Medical School, Zhejiang University, 88 Jie Fang Road, Hangzhou, 310009, China. drshaoplastic@126.com.
Zheren
Z
Shao
D055372:AMP-Activated Protein Kinases / Q000037:antagonists & inhibitors*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D000076222:Mechanistic Target of Rapamycin Complex 1; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D046912:Multiprotein Complexes / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
D000970:Antineoplastic Agents; D046912:Multiprotein Complexes; D047428:Protein Kinase Inhibitors; D000076222:Mechanistic Target of Rapamycin Complex 1; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases
AMPK; Compound 13; Melanoma; mTORC1 and proliferation