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

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

Oncotarget. 2017 Dec 08;8(64):108006-108019

Authors: Chen JC, Hsieh MC, Lin SH, Lin CC, Hsi YT, Lo YS, Chuang YC, Hsieh MJ, Chen MK

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.

PMID: 29296219 [PubMed]

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