A Novel Chalcone derivative suppresses Melanoma cell growth through targeting Fyn/Stat3 pathway

Fyn has been documented to have oncogenic characteristics in multiple tumors, which might be a potential therapeutic target. Our finding showed that Fyn is overexpressed in melanoma cells and knock down of Fyn suppresses the proliferation of melanoma cells. To identify the potential inhibitors of Fyn, our in-house library including total of 11277 chemicals was conducted to vitro screening, among those compounds, eighty-three inhibitors were further examined to determine the effect on melanoma cells growth. A novel chalcone derivative Lj-1-60 exhibited low cellular toxicity and high anti-tumor efficacy. Moreover, Lj-1-60 suppresses the proliferation of melanoma in vitro and in vivo through inducing cell cycle arrest and apoptosis. Interestingly, Lj-1-60 directly associates with Fyn, as a consequence, inhibits the Fyn kinase activity. Stat3 is a well-known down stream transcriptional factor which plays a critical role in carcinogenesis including melanoma. The activation of Stat3 had been abrogated both in Lj-1-60 treated melanoma cells or Fyn knocking down cells. Taken together, our study revealed a novel Fyn inhibitor could significantly suppress melanoma growth, which is a promising potential inhibitor for melanoma treatment.