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
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Jui-Chieh Chen1,*, Ming-Ju Hsieh2,3,4,*, Chih-Jung Chen5,6,7, Jen-Tsun Lin8, Yu-Sheng Lo2, Yi-Ching Chuang2, Su-Yu Chien9,10,11, Mu-Kuan Chen12
1Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan
2Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan
3School of Optometry, Chung Shan Medical University, Taichung, Taiwan
4Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
5Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan
6Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan
7School of Medicine, Chung Shan Medical University, Taichung, Taiwan
8Hematology & Oncology, Changhua Christian Hospital, Changhua, Taiwan
9Department of Pharmacy, Changhua Christian Hospital, Changhua, Taiwan
10College of Health Sciences, Chang Jung Christian University, Tainan, Taiwan
11Center for General Education, Mingdao University, Changhua, Taiwan
12Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan
*These authors have contributed equally to this work
Su-Yu Chien, email: email@example.com
Mu-Kuan Chen, email: firstname.lastname@example.org
Keywords: Polyphyllin G, nasopharyngeal carcinoma, apoptosis, autophagy, MAPK
Received: March 22, 2016 Accepted: August 24, 2016 Published: September 02, 2016
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.
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