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.