Polyphyllin G induces apoptosis and autophagy cell death in human oral cancer cells

Background: Polyphyllin G (also called polyphyllin VII), extract from rhizomes of Paris yunnanensis Franch, has been shown to have strong Anticancer activities in a wide variety of human Cancer cell lines. However, the underlying influences of Autophagy in human oral squamous cell carcinoma (OSCC) remain unclear.

Methods: In this study, the roles of Apoptosis and Autophagy in polyphyllin G-induced death in human oral Cancer cells were investigated. Moreover, the molecular mechanism of the Anticancer effects of polyphyllin G in human oral Cancer cells was investigated.

Results: The results revealed that polyphyllin G significantly inhibited cell proliferation in human oral Cancer cells; it dose-dependently induced Apoptosis in SAS and OECM-1 cells through Caspase-3, -8, and -9 activation and poly (ADP-ribose) polymerase cleavage. In addition, changes were observed in Bcl-2 and proapoptosis-related protein expression in different human oral Cancer cell lines. The expression of both LC3-II and beclin-1 was markedly increased, suggesting the induction of Autophagy in polyphyllin G-treated oral cells. To further clarify whether polyphyllin G-induced Apoptosis and Autophagy depended on Akt/extracellular signal-regulated kinases (ERK)/c-Jun N-terminal kinases (JNK)/p38 mitogen-activated protein kinases (MAPK) signaling pathways, the cells were cotreated with inhibitors. The results demonstrated polyphyllin G-induced Apoptosis in oral cells through the activation of ERK, Akt, p38 MAPK, and JNK, whereas ERK and JNK accounted for polyphyllin G-induced Autophagy.

Conclusion: This study is the first to demonstrate Apoptosis and Autophagy during polyphyllin G-induced cell death in human oral Cancer cell lines. These results suggest that polyphyllin G is a promising candidate for developing antitumor drugs targeting human oral squamous cell carcinoma.