title: (-)-Epigallocatechin-3-gallate suppresses growth of AZ521 human gastric cancer cells by targeting the DEAD-box RNA helicase p68.
abstract: (-)-Epigallocatechin-3-gallate (EGCG), the most abundant and biologically active polyphenol in green tea, induces apoptosis and suppresses proliferation of cancer cells by modulating multiple signal transduction pathways. However, the fundamental mechanisms responsible for these cancer-preventive effects have not been clearly elucidated. Recently, we found that EGCG can covalently bind to cysteine residues in proteins through autoxidation and subsequently modulate protein function. In this study, we demonstrate the direct binding of EGCG to cellular proteins in AZ521 human gastric cancer cells by redox-cycle staining. We comprehensively explored the binding targets of EGCG from EGCG-treated AZ521 cells by proteomics techniques combined with the boronate-affinity pull-down method. The DEAD-box RNA helicase p68, which is overexpressed in a variety of tumor cells and plays an important role in cancer development and progression, was identified as a novel EGCG-binding target. Exposure of AZ521 cells to EGCG lowered the p68 level dose dependently. The present findings show that EGCG inhibits AZ521 cell proliferation by preventing β-catenin oncogenic signaling through proteasomal degradation of p68 and provide a new perspective on the molecular mechanism of EGCG action.
authors.affiliation: Department of Biological Chemistry, Division of Applied Life Science, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Naka-ku, Sakai 599-8531, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Tanaka
authors.forename: Takeshi
authors.initials: T
authors.lastname: Ishii
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mizuno
authors.forename: Taiki
authors.initials: T
authors.lastname: Mori
authors.forename: Ryoichi
authors.initials: R
authors.lastname: Yamaji
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Nakamura
authors.forename: Shigenori
authors.initials: S
authors.lastname: Kumazawa
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Nakayama
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Akagawa
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D053487:DEAD-box RNA Helicases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008968:Molecular Conformation; D013237:Stereoisomerism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D002392:Catechin; C045651:epigallocatechin gallate; D053487:DEAD-box RNA Helicases