Polyphyllin G induce apoptosis and autophagy in human nasopharyngeal cancer cells by modulation of AKT and mitogen-activated protein kinase pathways in vitro and in vivo.
Polyphyllin G (also call polyphyllin VII), extract from rhizomes of Paris yunnanensis Franch, has been demonstrated to have strong anticancer activities in a wide variety of human cancer cell lines. Previous studies found that Polyphyllin G induced apoptotic cell death in human hepatoblastoma cancer and lung cancer cells. However, the underlying mechanisms of autophagy in human nasopharyngeal carcinoma (NPC) remain unclear. In this study, Polyphyllin G can potently induced apoptosis dependent on the activations of caspase-8, -3, and -9 and the changes of Bcl-2, Bcl-xL and Bax protein expression in different human NPC cell lines (HONE-1 and NPC-039). The amount of both LC3-II and Beclin-1 was intriguingly increased suggest that autophagy was induced in Polyphyllin G-treated NPC cells. To further clarify whether Polyphyllin G-induced apoptosis and autophagy depended on AKT/ERK/JNK/p38 MAPK signaling pathways, cells were combined treated with AKT inhibitor (LY294002), ERK1/2 inhibitor (U0126), p38 MAPK inhibitor (SB203580), or JNK inhibitor (SP600125). These results demonstrated that Polyphyllin G induced apoptosis in NPC cells through activation of ERK, while AKT, p38 MAPK and JNK were responsible for Polyphyllin G-induced autophagy. Finally, an administration of Polyphyllin G effectively suppressed the tumor growth in the NPC carcinoma xenograft model in vivo. In conclusion, our results reveal that Polyphyllin G inhibits cell viability and induces apoptosis and autophagy in NPC cancer cells, suggesting that Polyphyllin G is an attractive candidate for tumor therapies. Polyphyllin G may promise candidate for development of antitumor drugs targeting nasopharyngeal carcinoma.
Department of Biochemical Science and Technology, National Chiayi University, Chiayi 600, Taiwan.
Jui-Chieh
JC
Chen
Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.|School of Optometry, Chung Shan Medical University, Taichung 40201, Taiwan.|Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan.
Ming-Ju
MJ
Hsieh
Department of Surgical Pathology, Changhua Christian Hospital, Changhua 500, Taiwan.|Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.|School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan.
Chih-Jung
CJ
Chen
Hematology & Oncology, Changhua Christian Hospital, Changhua 500, Taiwan.
Jen-Tsun
JT
Lin
Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
Yu-Sheng
YS
Lo
Cancer Research Center, Changhua Christian Hospital, Changhua 500, Taiwan.
Yi-Ching
YC
Chuang
Department of Pharmacy, Changhua Christian Hospital, Changhua 500, Taiwan.|College of Health Sciences, Chang Jung Christian University, Tainan 71101, Taiwan.|Center for General Education, Mingdao University, Changhua 52345, Taiwan.
Su-Yu
SY
Chien
Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua 500, Taiwan.
Mu-Kuan
MK
Chen
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000502:physiology; D012503:Saponins / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism
D012503:Saponins; C585643:polyphyllin VII; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D020928:Mitogen-Activated Protein Kinases
MAPK; Polyphyllin G; apoptosis; autophagy; nasopharyngeal carcinoma