Oncotarget

Research Papers:

Coronarin D induces reactive oxygen species-mediated cell death in human nasopharyngeal cancer cells through inhibition of p38 MAPK and activation of JNK

Jui-Chieh Chen, Ming-Chang Hsieh, Shu-Hui Lin, Chia-Chieh Lin, Yi-Ting Hsi, Yu-Sheng Lo, Yi-Ching Chuang, Ming-Ju Hsieh and Mu-Kuan Chen _

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Oncotarget. 2017; 8:108006-108019. https://doi.org/10.18632/oncotarget.22444

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Abstract

Jui-Chieh Chen1,*, Ming-Chang Hsieh2,3,*, Shu-Hui Lin4, Chia-Chieh Lin5, Yi-Ting Hsi5, Yu-Sheng Lo5, Yi-Ching Chuang5, Ming-Ju Hsieh5,6 and Mu-Kuan Chen7

1Department of Biochemical Science and Technology, National Chiayi University, Chiayi, Taiwan

2School of Medical Laboratory and Biotechnology, Chung Shan Medical University, Taichung, Taiwan

3Department of Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan

4Department of Surgical Pathology, Changhua Christian Hospital, Changhua, Taiwan

5Cancer Research Center, Changhua Christian Hospital, Changhua, Taiwan

6Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

7Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan

*These authors have contributed equally to this work

Correspondence to:

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

Ming-Ju Hsieh, email: 170780@cch.org.tw

Keywords: Coronarin D; nasopharyngeal carcinoma; apoptosis; autophagy

Received: September 01, 2017     Accepted: October 28, 2017     Published: November 14, 2017

ABSTRACT

Background and Purpose: Nasopharyngeal carcinoma (NPC) belongs to squamous cell carcinoma that occurs in the epithelial lining of the nasopharynx. Because of the anatomical position close to the cervical lymph node, some patients have a distant metastasis at the time of diagnosis that leads to treatment failure. Although early stages have a high curability and excellent prognosis, advanced NPC urgently requires new drugs developed to reinforce the effectiveness of therapy without noticeable side effects.

Experimental approach: Coronarin D (CD), a natural product extracted from the rhizomes of Hedychium coronarium, has been reported to possess anticancer potential. The aim of the present study was to determine the anticancer activity of CD and further elucidate the underlying molecular mechanisms.

Key Results: In this study, we first demonstrated that CD potently suppressed cell viability in various NPC cell lines. Treatment of cells with CD induced G2/M arrest, apoptosis, and autophagy. Further studies showed that CD increased the production of reactive oxygen species and subsequently activated both autophagy and apoptosis. Moreover, we found that CD-induced activation of p38 and JNK constituted major mechanisms involved in the apoptosis and autophagy triggered by CD. In particular, inhibition of autophagy could strengthen the cytotoxicity of CD, implying that autophagy seems to play a valuable survival and protective role in cancer cells.

Conclusions & Implications: These findings provide a promise for the use of CD in combination with autophagy inhibitors for treatment of human NPC cell lines.


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