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

研究成果: 雜誌貢獻文章

61 引文 (Scopus)

摘要

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.
原文英語
頁(從 - 到)1247-1258
頁數12
期刊Molecular Nutrition and Food Research
56
發行號8
DOIs
出版狀態已發佈 - 八月 2012
對外發佈Yes

指紋

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

ASJC Scopus subject areas

  • Food Science
  • Biotechnology

引用此文

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.

於: Molecular Nutrition and Food Research, 卷 56, 編號 8, 08.2012, p. 1247-1258.

研究成果: 雜誌貢獻文章

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

AU - Chou, Ming Yung

AU - Yu, Cheng Chia

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N2 - 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.

AB - 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.

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