Oncotarget

Research Papers:

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

Jui-Chieh Chen, Ming-Ju Hsieh, Chih-Jung Chen, Jen-Tsun Lin, Yu-Sheng Lo, Yi-Ching Chuang, Su-Yu Chien _ and Mu-Kuan Chen

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Oncotarget. 2016; 7:70276-70289. https://doi.org/10.18632/oncotarget.11839

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Abstract

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

Correspondence to:

Su-Yu Chien, email: 2655@cch.org.tw

Mu-Kuan Chen, email: 53780@cch.org.tw

Keywords: Polyphyllin G, nasopharyngeal carcinoma, apoptosis, autophagy, MAPK

Received: March 22, 2016    Accepted: August 24, 2016    Published: September 02, 2016

ABSTRACT

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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