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Impairment of tumor‐initiating stem‐like property and reversal of epithelial–mesenchymal transdifferentiation in head and neck cancer by resveratrol treatment
Author(s) -
Hu FangWei,
Tsai LoLin,
Yu ChuanHang,
Chen PeiNi,
Chou MingYung,
Yu ChengChia
Publication year - 2012
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200150
Subject(s) - resveratrol , epithelial–mesenchymal transition , cancer research , cd44 , homeobox protein nanog , slug , head and neck cancer , in vivo , bmi1 , vimentin , cancer , mesenchymal stem cell , nestin , cancer stem cell , medicine , chemistry , stem cell , biology , pathology , pharmacology , in vitro , metastasis , immunohistochemistry , microbiology and biotechnology , neural stem cell , embryonic stem cell , biochemistry , gene , induced pluripotent stem cell
Scope Recent reports have demonstrated that head and neck cancer‐derived tumor‐initiating cells (HNC‐TICs) presented high tumorigenic, chemoradioresistant, metastatic properties, and were coupled with gain of epithelial–mesenchymal transition (EMT) characteristics. The aim of this study was to investigate the chemotherapeutic effect and regulatory mechanisms of resveratrol on HNC‐TICs. Methods and results We first observed that the treatment of resveratrol significantly downregulated the ALDH1 activity and CD44 positivity of head and neck cancer (HNC) cells in a dose‐dependent manner ( p < 0.05). Moreover, resveratrol treatment reduced self‐renewal property and stemness genes signatures (Oct4, Nanog, and Nestin) expression in sphere‐forming HNC‐TICs. Additionally, the repressive effect of resveratrol on in vitro malignant properties including invasiveness/anchorage‐independent growth was mediated by regulating productions of EMT markers Slug, ZEB1, N‐cadherin, E‐cadherin, and Vimentin. Importantly, an in vivo nude mice model showed that resveratrol treatment to xenograft tumors by oral gavage reduced tumor growth, stemness, and EMT markers in vivo. Lastly, synergistic effect of resveratrol and conventional chemotreatment attenuated tumor‐initiating cells property in HNC‐TICs. Conclusions Our results demonstrated that resveratrol would be a valuable therapeutics clinically in combination with conventional chemotherapy treatment modalities for malignant HNCs by elimination of tumor‐initiating stem‐like and EMT properties.