Impairment of tumor-initiating stem-like property and reversal of epithelial-mesenchymal transdifferentiation in head and neck cancer by resveratrol treatment

Fang Wei Hu, Lo Lin Tsai, Chuan Hang Yu, Pei Ni Chen, Ming Yung Chou, Cheng Chia Yu

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1247-1258
Number of pages12
JournalMolecular Nutrition and Food Research
Volume56
Issue number8
DOIs
Publication statusPublished - Aug 2012
Externally publishedYes

Fingerprint

resveratrol
Head and Neck Neoplasms
Neoplastic Stem Cells
Epithelial-Mesenchymal Transition
neoplasms
stems
Neoplasms
cadherins
Cadherins
Therapeutics
Nestin
Gastropoda
vimentin
slugs
Vimentin
Growth
head and neck neoplasms
Heterografts
Nude Mice
neck

Keywords

  • Cancer Stem Cells
  • Epithelial-mesenchymal transition
  • Head and neck cancer
  • Resveratrol
  • Tumor-initiating cells

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

Cite this

Impairment of tumor-initiating stem-like property and reversal of epithelial-mesenchymal transdifferentiation in head and neck cancer by resveratrol treatment. / Hu, Fang Wei; Tsai, Lo Lin; Yu, Chuan Hang; Chen, Pei Ni; Chou, Ming Yung; Yu, Cheng Chia.

In: Molecular Nutrition and Food Research, Vol. 56, No. 8, 08.2012, p. 1247-1258.

Research output: Contribution to journalArticle

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