title: Chronic administration of green tea extract to TRAMP mice induces the collapse of Golgi apparatus in prostate secretory cells and results in alterations of protein post-translational processing.
abstract: Considering its long latency, prostate cancer (PCa) represents an ideal target for chemoprevention strategies. Green tea extract (GTE) has been proved to be one of the most promising natural substances capable of inhibiting PCa progression in animal models (transgenic adenocarcinoma of mouse prostate), as well as in humans. However, the cellular targets of the GTE action are mostly unknown. The main objective of this work was to investigate whether the endoplasmic reticulum (ER) and the Golgi apparatus (GA), known to be actively involved in sensing stress stimuli and initiating and propagating cell death signalling, may represent the subcellular targets of GTE action. To this end, 42 TRAMP mice were divided into four experimental groups: groups II and IV, received GTE in tap water (0.3 g/100 ml solution) starting at 8 weeks of age and up to the time of sacrifice. Groups I and III were respective age-matched water-fed controls. The animals were sacrificed after 4 weeks (groups I and II) or 40 weeks of treatment (groups II and IV). We also treated TRAMP-C2 cells with GTE (20 µg/ml for 7 days) to check the expression profile of clusterin (CLU), a protein involved in prostate tumourigenesis, extensively processed through ER-GA before being secreted through the plasma membrane. In vivo we found that chronic administration of GTE in TRAMP mice results in collapse of ER and GA in prostate epithelial cells. Consistently, in vitro we found that the mature, fully processed form of CLU, sCLU, is strongly reduced by GTE treatment in TRAMP-C2 cells. Taking into account the sCLU biogenesis dependence on the ER-GA integrity and the proposed anti-apoptotic role of sCLU, the possibility for GTE to counteract PCa progression by interfering with sCLU biogenesis is suggested.
authors.affiliation: Department of Biomedical Sciences, University of Modena and Reggio Emilia, I-41100 Modena, Italy.
authors.forename: Pierpaola
authors.initials: P
authors.lastname: Davalli
authors.forename: Federica
authors.initials: F
authors.lastname: Rizzi
authors.forename: Gaetano Felice
authors.initials: GF
authors.lastname: Caldara
authors.forename: Serena
authors.initials: S
authors.lastname: Davoli
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Corti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Silva
authors.forename: Serenella
authors.initials: S
authors.lastname: Astancolle
authors.forename: Marco
authors.initials: M
authors.lastname: Vitale
authors.forename: Saverio
authors.initials: S
authors.lastname: Bettuzzi
authors.forename: Marialuisa
authors.initials: M
authors.lastname: Arcari
authors.forename: Giacomo
authors.initials: G
authors.lastname: Azzali
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000648:ultrastructure; D000818:Animals; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D051152:Clusterin / Q000378:metabolism; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000648:ultrastructure; D006056:Golgi Apparatus / Q000187:drug effects* / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000648:ultrastructure; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D013662:Tea / Q000737:chemistry
chemical_list: D051152:Clusterin; D013662:Tea; D002392:Catechin; C472086:polyphenon E