Pinocembrin induces ER stress mediated apoptosis and suppresses autophagy in melanoma cells

Abstract

Melanoma, one of the toughest tumors to treat, features high metastasis and high lethality. Pinocembrin is a natural flavanone with versatile biological and pharmacological activities. Here, we evaluated the anti-tumor effects of pinocembrin against melanoma in vitro and in vivo. In vitro, pinocembrin inhibited the proliferation of melanoma cells (B16F10 and A375) in a dose-dependent manner. It induced endoplasmic reticulum stress via IRE1α/Xbp1 pathway and triggered caspase-12/-4 mediated apoptosis in both cell lines. Furthermore, we discovered that pinocembrin suppressed autophagy through the activation of PI3K/Akt/mTOR pathway, which serves as a dual mechanism to enhance the pro-death effect of pinocembrin. In vivo, pinocembrin inhibited the growth of B16F10 by inducing apoptosis. Taken together, our results demonstrated that pinocembrin can induce ER stress mediated apoptosis and suppress autophagy in melanoma, indicating its application potential for melanoma therapy.

Keywords: Apoptosis; Autophagy; ER stress; Melanoma; Pinocembrin.