Platycodin-D exerts its anti-cancer effect by promoting c-Myc protein ubiquitination and degradation in gastric cancer.

Abstract

Platycodin D (PD) is a triterpene saponin extracted from the root of Platycodon grandiflorum. It has been reported to exhibit multiple pharmacological and biological properties. There is substantial evidence to support that PD displays a wide range of anti-tumor activities. However, the detailed molecular mechanism still needs further elaboration. In the present study, to explore whether PD inhibits gastric cancer (GC) cell viability, eightGCcell lines and the GES-1 cell line (a gastric mucosal cell line) were tested. We found that PD exhibited better inhibitory activity on GCcell lines than on the non-tumor cell line. Besides, treatment with PD led to a significant cell cycle arrest, thereby causing subsequent apoptosis. Regarding the cell growth inhibition mechanism, PD can downregulate the protein level of c-Myc rather than its mRNA level in a dose-dependent manner. Further studies revealed that PD disturbed the overall ubiquitination level in GCcell lines and enhanced the ubiquitination-dependent degradation of c-Myc. Interestingly, the inhibition of cell viability by PD could be restored to a certain extent when the expression of c-Myc was recovered, suggesting that PD-mediated GCcell growth inhibition is closely associated with c-Myc expression. Our study proposes a novel molecular mechanism for PD inhibiting GCcell proliferation and growth by destabilizing the c-Myc protein. This work may lay a preliminary foundation for developing PD as an anti-cancer therapy.