• Ming-Ju Hsieh, Su-Yu Chien, Jen-Tsun Lin, Shun-Fa Yang, and Mu-Kuan Chen.
• Cancer Research Center, Changhua Christian Hospital, Changhua, 50006, Taiwan; School of Optometry, Chung Shan Medical University, Taichung, 40201, Taiwan; Graduate Institute of Biomedical Sciences, China Medical University, Taichung, 404, Taiwan. Electronic address: 170780@cch.org.tw.
• Phytomedicine. 2016 Dec 1; 23 (13): 1545-1554.

BackgroundPolyphyllin 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.MethodsIn 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.ResultsThe 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.ConclusionThis 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.Copyright © 2016 Elsevier GmbH. All rights reserved.

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