Bavachinin Suppresses the Growth of Melanoma Cells by <scp>eEF2K</scp> / <scp>eEF2</scp> Signaling and Induces Autophagy

Melanoma, a formidable adversary in the realm of cancer, poses a significantly deadly public health challenge globally. Eukaryotic elongation factor 2 kinase (eEF2K), as a promising and attractive therapeutic target for cancer, was reported to be related to poor patient survival and prognosis. Bavachinin (BVC), a natural compound isolated from Psoralea corylifolia L., was reported to have an anti-cancer effect. However, the effect and underlying mechanisms of BVC on the metastasis of melanoma are certainly unclear. In this experiment, the aim was to investigate the suppressive action of BVC on melanoma growth and metastasis, as well as the underlying mechanisms. The proliferation, cell migration, and invasion, cell cycle, and cell apoptosis in vitro were determined using CCK8, EdU staining, transwell assays, and Western blotting, respectively. The amount of eEF2K signaling-related proteins was detected by Western blotting and immunofluorescence. The interaction between BVC and eEF2K was performed by molecular docking and molecular dynamics. The eEF2K lentivirus transfection was conducted to overexpress eEF2K and explore its function in BVC's anti-melanoma action. Finally, using mouse allograft melanoma models, the action of BVC on melanoma growth was validated in vivo. BVC suppressed cell proliferation, caused cell cycle arrest, promoted cell apoptosis, and restrained migration and invasion. Interestingly, BVC induced autophagy, and suppressing autophagy partially enhanced the anti-tumor effect of BVC. Of note, BVC directly bound to eEF2K and inhibited the eEF2K/eEF2 signaling pathway in melanoma cells. In addition, eEF2K overexpression by lentivirus partly limited the antitumor effects of BVC. Finally, the allograft mouse models ulteriorly validated that BVC impaired tumor growth and inhibited eEF2K signaling in vivo. Collectively, the present study demonstrated that BVC inhibited melanoma metastasis by targeting eEF2K/eEF2 signaling, and the inhibition of autophagy caused by BVC could further contribute to the anti-melanoma potency of BVC.