title: Concomitant inhibition of HSP90, its mitochondrial localized homologue TRAP1 and HSP27 by green tea in pancreatic cancer HPAF-II cells.
abstract: Pancreatic cancer is a deadly disease characterized by poor prognosis and patient survival. Green tea polyphenols have been shown to exhibit multiple antitumor activities in various cancers, but studies on the pancreatic cancer are very limited. To identify the cellular targets of green tea action, we exposed a green tea extract (GTE) to human pancreatic ductal adenocarcinoma HPAF-II cells and performed two-dimensional gel electrophoresis of the cell lysates. We identified 32 proteins with significantly altered expression levels. These proteins are involved in drug resistance, gene regulation, motility, detoxification and metabolism of cancer cells. In particular, we found GTE inhibited molecular chaperones heat-shock protein 90 (Hsp90), its mitochondrial localized homologue Hsp75 (tumor necrosis factor receptor-associated protein 1, or Trap1) and heat-shock protein 27 (Hsp27) concomitantly. Western blot analysis confirmed the inhibition of Hsp90, Hsp75 and Hsp27 by GTE, but increased phosphorylation of Ser78 of Hsp27. Furthermore, we showed that GTE inhibited Akt activation and the levels of mutant p53 protein, and induced apoptosis and growth suppression of the cells. Our study has identified multiple new molecular targets of GTE and provided further evidence on the anticancer activity of green tea in pancreatic cancer.
authors: Department of Medicine, University of California, Los Angeles, CA 90095, USA.
authors: Lifeng
authors: L
authors: Zhang
authors: Eric
authors: E
authors: Pang
authors: Rachel R Ogorzalek
authors: RR
authors: Loo
authors: Jianyu
authors: J
authors: Rao
authors: Vay-Liang W
authors: VL
authors: Go
authors: Joseph A
authors: JA
authors: Loo
authors: Qing-Yi
authors: QY
authors: Lu
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D028241:Camellia sinensis / Q000737:chemistry*; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D010190:Pancreatic Neoplasms / Q000378:metabolism; D010936:Plant Extracts / Q000494:pharmacology*; D059808:Polyphenols / Q000494:pharmacology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D055551:HSP27 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D010936:Plant Extracts; D059808:Polyphenols; C092306:TRAP1 protein, human; D016159:Tumor Suppressor Protein p53; D051057:Proto-Oncogene Proteins c-akt