Molecular mechanism of epigallocatechin-3-gallate in human esophageal squamous cell carcinoma in vitro and in vivo

Liu,Lifeng; Hou,Lei; Gu,Shanzhi; Zuo,Xiaoxiao; Meng,Du; Luo,Minna; Zhang,Xiaojin; Huang,Shangke; Zhao,Xinhan

doi:10.3892/or.2014.3555

Molecular mechanism of epigallocatechin-3-gallate in human esophageal squamous cell carcinoma in vitro and in vivo

Authors:
- Lifeng Liu
- Lei Hou
- Shanzhi Gu
- Xiaoxiao Zuo
- Du Meng
- Minna Luo
- Xiaojin Zhang
- Shangke Huang
- Xinhan Zhao
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Affiliations: Department of Otolaryngology-Head and Neck Surgery, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China, Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China, Department of Forensic Medicine, Medical School of Xi'an Jiaotong University, Xi’an, Shaanxi 710061, P.R. China, Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China
Published online on: October 20, 2014 https://doi.org/10.3892/or.2014.3555
Pages: 297-303

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Abstract

Epigallocatechin-3-gallate (EGCG), the major polyphenol of green tea, has been shown to inhibit proliferation in various types of tumors. However, few studies concerning the role and mechanism of EGCG in esophageal squamous cell carcinoma are available. Therefore, the antitumor mechanism of EGCG needs to be investigated. The present study aimed to examine the antitumor effect of EGCG on the human esophageal squamous cell carcinoma cell lines, Eca-109 and Te-1, in vitro and in vivo. Cell viability was assessed using the MTT assay and tumor formation and growth in murine xenograft models with or without EGCG treatment. Cell cycle analysis and levels of reactive oxygen species (ROS) were detected using flow cytometry. Apoptosis was measured by Annexin/propidium iodide staining. Caspase-3 cleavage and vascular endothelial growth factor (VEGF) expression were detected using western blot analysis and immunohistochemistry in tumor cell lines and tumor xenografts, respectively. The results showed that EGCG inhibited proliferation in the Eca-109 and Te-1 cells in a time- and dose-dependent manner. Tumor cells were arrested in the G1 phase and apoptosis was accompanied by ROS production and caspase-3 cleavage. In a mouse model, EGCG significantly inhibited the growth of Eca-109 tumors by increasing the expression of cleaved-caspase-3 and decreasing VEGF protein levels. Taken together, the results suggest that EGCG inhibits proliferation and induces apoptosis through ROS production, caspase-3 activation, and a decrease in VEGF expression in vitro and in vivo. Furthermore, EGCG may have future clinical applications for novel approaches to treat esophageal squamous cell carcinoma.

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