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

doi:10.18632/oncotarget.22444

Abstract

Background and PurposeNasopharyngeal 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 approachCoronarin 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 ResultsIn 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 & ImplicationsThese findings provide a promise for the use of CD in combination with autophagy inhibitors for treatment of human NPC cell lines.

Highlights

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer arising from the epithelial cells lining the nasopharynx
Conclusions & Implications: These findings provide a promise for the use of Coronarin D (CD) in combination with autophagy inhibitors for treatment of human NPC cell lines
These results demonstrate that NAC simultaneously reduces CD-induced autophagy and apoptosis, which regulates their balance and thereby partially promotes CD-induced cell death in NPC cells

Summary

Introduction

Nasopharyngeal carcinoma (NPC) is a type of head and neck cancer arising from the epithelial cells lining the nasopharynx. Due to the anatomical position of NPC close to the cervical lymph node, it is more likely to metastasize to other areas of the body, leading to difficulty in the use of surgery for treatment. The use of concomitant chemotherapy and radiotherapy has been shown to improve survival in patients with advanced NPC [4]. These therapies still produce severe adverse effects [5, 6]. The development of new treatment modalities is urgently required to reduce side effects and to reinforce the effectiveness of therapy in NPC. 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. The aim of the present study was to determine the anticancer activity of CD and further elucidate the underlying molecular mechanisms

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Results

Conclusion