Lycopene differentially induces quiescence and apoptosis in androgen-responsive and -independent prostate cancer cell lines.
OBJECTIVE
Lycopene has been credited with a number of health benefits including a decrease in prostate cancer risk. Our study investigates the molecular mechanism underlying anti-cancer activity of lycopene-based products in androgen-responsive (LNCaP) and androgen-independent (PC3) cells.


METHODS
The effect of lycopene-based agents on prostate cancer growth and survival were examined using proliferation assays, bromodeoxyuridine incorporation and flow cytometric analysis of cellular DNA content. Biochemical effects of lycopene treatment were investigated by immunoblotting for changes in the absolute levels and phosphorylation states of cell cycle regulatory and signalling proteins.


RESULTS
LNCaP and PC3 cells treated with the lycopene-based agents undergo mitotic arrest, accumulating in G0/G1 phase. Immunoblot screening indicated that lycopene's antiproliferative effects are likely achieved through a block in G1/S transition mediated by decreased levels of cyclins D1 and E and cyclin dependent kinase 4 and suppressed Retinoblastoma phosphorylation. These responses correlated with decreased insulin-like growth factor-I receptor expression and activation, increased insulin-like growth factor binding protein 2 expression and decreased AKT activation. Exposure to lycopene at doses as low as 10 nM for 48 h induced a profound apoptotic response in LNCaP cells. In contrast PC3 cells were resistant to apoptosis at doses up to 1 microM.


CONCLUSIONS
Lycopene exposure can suppress phosphatidylinositol 3-kinase-dependent proliferative and survival signalling in androgen-responsive LNCaP and androgen-independent PC3 cells suggesting that the molecular mechanisms for the cytostatic and cytotoxic actions of lycopene involve induction of G0/G1 cell cycle arrest. This study supports further examination of lycopene as a potential agent for both the prevention and treatment of prostate cancer.
Ivanov
Nikita I
NI
Prostate Research Centre at Vancouver General Hospital, University of British Columbia, 2660 Oak Street, Vancouver, BC, Canada V6T 1Z4.
Cowell
Simon P
SP
Brown
Paula
P
Rennie
Paul S
PS
Guns
Emma S
ES
Cox
Michael E
ME
D000728:Androgens / Q000378:metabolism / Q000494:pharmacology; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002338:Carotenoids / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D000077276:Lycopene; D008297:Male; D010766:Phosphorylation; D011471:Prostatic Neoplasms; D016192:Resting Phase, Cell Cycle / Q000187:drug effects
D000728:Androgens; D016588:Anticarcinogenic Agents; D002338:Carotenoids; D000077276:Lycopene