Podocarpusflavone A inhibits cell growth of skin cutaneous melanoma by suppressing STAT3 signaling

•PCFA exhibited potent inhibitory effects on melanoma both in vitro and in vivo.•PCFA inhibited the activation of STAT3 through suppressing the phosphorylation of JAK2.•PCFA inhibits melanoma growth via the inhibition of JAK2/STAT3 pathway. JAK2/STAT3 pathway is involved in the development and progression of melanoma once DNA damage is caused by environment and genetic factors. Here, we aimed to identify novel inhibitor of JAK2/STAT3 pathway and reveal the underlying mechanisms. Eighty MedChemExpress compounds were screened by using STAT3-Luc reporter in A375 cells. Podocarpusflavone A (PCFA) was identified as an inhibitor of STAT3, which was further verified in four melanoma cell lines. The anti-melanoma effects and mechanism of PCFA were examined and explored in melanoma cells and mouse xenograft models by using Western blot and cell-counting kit-8 assay. PCFA exhibited potent inhibitory effects on melanoma both in vitro and in vivo. PCFA inhibited the activation of STAT3 through suppressing the phosphorylation of JAK2, and then restrained cell cycle and induced apoptosis of melanoma cells. PCFA inhibits melanoma growth via the inhibition of JAK2/STAT3 pathway, which provides a promising therapeutic strategies of melanoma treatment.