Dual targeting of the p38 MAPK‐HO‐1 axis and cIAP1/XIAP by demethoxycurcumin triggers caspase‐mediated apoptotic cell death in oral squamous cell carcinoma cells

Ming Hsien Chien, Wei En Yang, Yi Chieh Yang, Chia Chi Ku, Wei Jiunn Lee, Meng Ying Tsai, Chiao Wen Lin, Shun Fa Yang

研究成果: 雜誌貢獻文章同行評審

4 引文 斯高帕斯(Scopus)

摘要

Demethoxycurcumin (DMC) is a curcumin analogue with better stability and higher aqueous solubility than curcumin after oral ingestion and has the potential to treat diverse cancers, including oral squamous cell carcinoma (OSCC). The aim of this study was to investigate the anticancer effects and underlying mechanisms of DMC against OSCC. We found that DMC suppressed cell proliferation via simultaneously inducing G2/M‐phase arrest and cell apoptosis. Mechanistic investigations found that the downregulation of cellular IAP 1 (cIAP1)/X‐chromosome-linked IAP (XIAP) and upregulation of heme oxygenase‐1 (HO‐1) were critical for DMC‐induced caspase‐8/‐9/‐3 activation and apoptotic cell death. Moreover, p38 mitogen‐activated protein kinase (MAPK) and c‐Jun N‐terminal kinase (JNK)1/2 were activated by DMC treatment in OSCC cells, and only the inhibition of p38 MAPK significantly abolished DMC‐induced HO‐1 expression and caspase‐8/‐9/‐3 activation. The analyses of clinical datasets revealed that patients with head and neck cancers expressing high HO‐1 and low cIAP1 had the most favorable prognoses. Furthermore, a combinatorial treatment of DMC with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, gefitinib, significantly enhanced the inhibitory effect of gefitinib on the proliferation of OSCC cells. Overall, the current study supported a role for DCM as part of a therapeutic approach for OSCC through suppressing IAPs and activating the p38‐HO‐1 axis.

原文英語
文章編號703
期刊Cancers
12
發行號3
DOIs
出版狀態已發佈 - 三月 2020

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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