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An androgen‐independent androgen receptor function protects from inositol hexakisphosphate toxicity in the PC3/PC3(AR) prostate cancer cell lines
Author(s) -
Diallo JeanSimon,
Péant Benjamin,
Lessard Laurent,
Delvoye Nathalie,
Le Page Cécile,
MesMasson AnneMarie,
Saad Fred
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20455
Subject(s) - androgen receptor , downregulation and upregulation , prostate cancer , androgen , endocrinology , cancer research , cell culture , medicine , receptor , inositol , biology , apoptosis , chemistry , cancer , biochemistry , gene , hormone , genetics
Abstract BACKGROUND Inositol hexakisphosphate (IP6) is a phytochemical exhibiting anticancer activity. Because few prostate cancer (PCa) cell lines have been used to study IP6, we assessed its efficacy in a panel of PCa cell lines. METHODS AND RESULTS Using WST‐1 assays we observed that, although androgens did not modulate its efficacy, IP6 was more active in androgen receptor (AR) negative cells than in AR‐positive cells. Stable expression of the AR in PC3 cells (PC3(AR)) decreased the response to IP6, which was reversed by an AR‐targeting siRNA. Furthermore, AR expression in PC3 cells resulted in significantly reduced caspase‐3 activation ( P < 0.001) and DNA fragmentation ( P < 0.05) in response to IP6. Similarly, although treatment with IP6 caused the upregulation of NF‐κB‐responsive (IκB‐α, IRF‐2) and p53/E2F‐responsive genes (Puma, Noxa) in PC3 cells, this increase was reduced in PC3AR cells ( P < 0.01). CONCLUSION We conclude that resistance to IP6 can be linked to a ligand‐independent AR function. Prostate © 2006 Wiley‐Liss, Inc.