Chronic administration of green tea extract to TRAMP mice induces the collapse ofGolgi apparatus in prostate secretory cells and results in alterations of proteinpost-translational processing

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.