Abstract
Abstract Recent reports have demonstrated that head and neck cancer derived tumor initiating cells (HNC-TICs) presented high tumorigenic, chemo-radioresistant, metastatic properties, and coupled with gain of epithelial-mesenchymal transition (EMT) characteristics. As curcumin, an active component of the spice turmeric, can exert cytotoxic effects on cancer cells without harming normal tissues. The aim of this study was to investigate the chemo-therapeutic effect and regulatory mechanisms of curcumin on HNC-TICs. We first observed that the treatment of curcumin significantly down-regulated the ALDH1 activity, CD44 positivity, self-renewal property, and side population of HNC cells in a dose dependent manner. Using miRNA/mRNA-microarray analysis, curcumin significantly increased expression of tumor suppressive miR-145. Further mechanistic studies showed that the re-expression of PU-PEI-mediated miR145 delivery led to decreased of TICs properties. Blocking of endogenous miR145 can dramatically enhance stemness and tumor-initiating properties in ALDH1-CD44- non-TICs HNC cells. Additionally, the repressive effect of miR-145 on TICs properties was mediated by regulating of EMT. Importantly, in vivo nude mice model showed that cucumin treatment by oral gavage or PU-PEI-mediated miR145 delivery to xenograft tumors reduced tumor growth and metastasis and prolonged the survival times of tumor-bearing mice. From these results, we conclude that the inhibition of tumor aggressiveness in HNC-TIC in by curcumin was in part was mediated by up-regulation of miR-145, suggesting that curcumin would be a valuable therapeutics clinically in treatment modalities for malignant head and neck cancers by elimination of tumor initiating stem-like, and EMT properties. Citation Format: Shih-Hwa Chiou, Guang-Yuh Chiou, Kai-Hsi Lu. Curcumin attenuates tumor initiating stem-like property of head and neck cancer through miR145 axis-mediated paracrine signaling. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 228. doi:10.1158/1538-7445.AM2013-228
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