title: Molecular mechanism of epigallocatechin-3-gallate in human esophageal squamous cell carcinoma in vitro and in vivo.
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.
authors.affiliation: 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.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Shaanxi Provincial People's Hospital, Xi'an, Shaanxi 710068, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Forensic Medicine, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Shanzhi
authors.initials: S
authors.lastname: Gu
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaoxiao
authors.initials: X
authors.lastname: Zuo
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Du
authors.initials: D
authors.lastname: Meng
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Minna
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Shangke
authors.initials: S
authors.lastname: Huang
authors.affiliation: Department of Medical Oncology, The First Affiliated Hospital of Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
authors.forename: Xinhan
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D053148:Caspase 3 / Q000378:metabolism; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004938:Esophageal Neoplasms / Q000188:drug therapy*; D000077277:Esophageal Squamous Cell Carcinoma; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017382:Reactive Oxygen Species; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D002392:Catechin; C045651:epigallocatechin gallate; C505407:CASP3 protein, human; D053148:Caspase 3