Beta-carotene modulates human prostate cancer cell growth and may undergo intracellular metabolism to retinol.
Epidemiologic and animal studies provide support for a relationship between high intakes of carotenoids from fruits and vegetables with reduced risk of several malignancies including prostate cancer. The highly controlled environments of in vitro systems provide an opportunity to investigate the cellular and molecular effects of carotenoids. The effects of beta-carotene (BC) on in vitro growth rates, p21(WAF1) and p53 gene expression, as well as the conversion of BC to retinol were investigated in three human prostate adenocarcinoma cell lines: PC-3, DU 145 and LNCaP. In these experiments, media concentrations of 30 micromol BC/L for 72 h significantly (P < 0.05) slowed in vitro growth rates in all three cell lines, independently of p53 or p21(WAF1) status or expression. (14)C-labeled retinol was detected in prostate tumor cells incubated with (14)C-labeled BC, suggesting metabolic conversion of BC to retinol. Conversely, no (14)C-labeled retinol was detected in media incubated without prostate cancer cells. These studies support a hypothesis that in vitro biological effects of BC on prostate cells may result in part from the conversion of BC to retinol or other metabolites. The possibility that prostate cancer cells in vivo locally metabolize provitamin A carotenoids to retinol and other related metabolites may have implications for our understanding of prostate cancer etiology and the design of future prevention studies.
Williams
A W
AW
Division of Nutritional Sciences and Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL 61801, USA.
Boileau
T W
TW
Zhou
J R
JR
Clinton
S K
SK
Erdman
J W
JW
D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014801:Vitamin A / Q000096:biosynthesis*; D019207:beta Carotene / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D019207:beta Carotene; D014801:Vitamin A