Abstract: | Gypenosides have anticancer activity against many cancers. Gypenoside LI is a gypenoside monomer from Gynostemma pentaphyllum, its pharmacological functions in melanoma have not been reported. In this study, we found that gypenoside LI had a potent cytotoxic effect on melanoma cells. Gypenoside LI can induce intrinsic apoptosis along with S phase arrest. Furthermore, gypenoside LI inhibited the colony formation ability of melanoma through inhibition of the Wnt/β‐catenin signaling pathway. Interestingly, we also found that gypenoside LI can induce the upregulation of the tumor suppressor miR‐128‐3p during melanoma apoptosis. In contrast, gypenoside LI induced apoptosis, cell cycle arrest, and inhibition of the Wnt/β‐catenin signaling pathway, which were abolished by overexpression of the miR‐128‐3p inhibitor in A375 cells. Taken together, these results showed that gypenoside LI could inhibit human melanoma cells through inducing apoptosis, arresting cell cycle at the S phase and suppressing the Wnt/β‐catenin signaling pathway in a miR‐128‐3p dependent manner. |