Icaritin, a novel FASN inhibitor, exerts anti-melanoma activities through IGF-1R/STAT3 signaling
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Jinfeng Wu1,2, Juan Du1, Xiuqiong Fu1, Bin Liu1,3, Huihui Cao1, Ting Li1, Tao Su1, Jinhua Xu2, Anfernee Kai-Wing Tse1, Zhi-Ling Yu1,4
1Center for Cancer and Inflammation Research, School of Chinese Medicine, Hong Kong Baptist University, Kowloon Tong, Hong Kong
2Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, China
3School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, China
4Institute of Integrated Bioinfomedicine and Translational Science, HKBU Shenzhen Research Institute and Continuing Education, Shenzhen, China
Anfernee Kai-Wing Tse, email: [email protected]
Zhi-Ling Yu, email: [email protected]
Keywords: icaritin, melanoma, STAT3, IGF-1R, FASN
Received: October 09, 2015 Accepted: May 25, 2016 Published: June 13, 2016
Icaritin (IT) is a flavonoid isolated from Herba Epimedii. In this study, we evaluated the anti-melanoma activities of IT, and determined its cytotoxic mechanism. We found that IT exerted cytotoxicity to melanoma cells. Furthermore, IT induced melanoma cell apoptosis, which was accompanied with PARP cleavage. Mechanistically, IT suppressed p-STAT3 (tyr705) level in parallel with increases of p-STAT3 (ser727), p-ERK and p-AKT. IT significantly inhibited STAT3 nuclear translocation and reduced the levels of STAT3 -targeted genes. IT also inhibited IGF-1-induced STAT3 activation through down-regulation of total IGF-1R level. No dramatic changes in IGF-1R mRNA levels were observed in IT-treated cells, suggesting that IT acted primarily at a post-transcriptional level. Using molecular docking analysis, IT was identified as a novel fatty acid synthase (FASN) inhibitor. We found that IT reduced the level of total IGF-1R via FASN inhibition. In summary, we reported that IT exerted anti-melanoma activities, and these effects were partially due to inhibition of FASN/IGF-1R/STAT3 signaling.
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