title: (-)-Epigallocatechin-3-gallate induces apoptosis in gastric cancer cell lines by down-regulating survivin expression.
abstract: The polyphenol (-)-epigallocatechin-3-gallate (EGCG) is a green tea constituent, which has been shown to inhibit cancer cell growth in vitro, in vivo and in epidemiological studies. In this study, we investigated its effects in gastric cancer cell lines. Five gastric cancer cell lines, the MKN-1, MKN-28, MKN-45, NUGC-3 and TMK-1, were found to be sensitive to EGCG treatment. Of all the cell lines tested, NUGC-3 was the most sensitive. EGCG treatment of NUGC-3 cells induced apoptosis, which was confirmed by sub-G1 analysis, caspase-Glo assay and Western blotting against cleaved PARP and cleaved caspase-3. EGCG treatment lowered survivin and increased Bax and TRAIL expression. Furthermore, EGCG induced p73 activation in NUGC-3 cells. Small interfering RNA against p73 diminished EGCG effects on survivin expression and cell viability. These results show that EGCG induces cell death in gastric cancer cells by apoptosis via inhibition of survivin expression downstream of p73. This study provides a novel mechanism whereby EGCG potentially inhibits cancer cell growth, concluding that EGCG may be a potential candidate in anti-survivin cancer therapy.
authors.affiliation: Department of Clinical Laboratory Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8543, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Onoda
authors.forename: Kageaki
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Shinya
authors.initials: S
authors.lastname: Nirasawa
authors.forename: Naoki
authors.initials: N
authors.lastname: Tsuji
authors.forename: Maki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kobayashi
authors.forename: Naoki
authors.initials: N
authors.lastname: Watanabe
mesh_terms: D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000502:physiology*; D015536:Down-Regulation; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics; D009687:Nuclear Proteins / Q000502:physiology*; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000077022:Survivin; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000502:physiology*
chemical_list: D016588:Anticarcinogenic Agents; C107489:BIRC5 protein, human; D004268:DNA-Binding Proteins; D051034:Inhibitor of Apoptosis Proteins; D009687:Nuclear Proteins; D000077022:Survivin; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins; D002392:Catechin; C045651:epigallocatechin gallate