Agents used for chemoprevention of prostate cancer may influence PSA secretion independently of cell growth in the LNCaP model of human prostate cancer progression.
BACKGROUND
The aim of this study was to evaluate the inhibitory growth effects of different potential chemopreventive agents in vitro and to determine their influence on PSA mRNA and protein expression with an established screening platform.


METHODS
LNCaP and C4-2 cells were incubated with genistein, seleno-L-methionine, lycopene, DL-alpha-tocopherol, and trans-beta-carotene at three different concentrations and cell growth was determined by the MTT assay. PSA mRNA expression was assessed by quantitative real-time RT-PCR and secreted PSA protein levels were quantified by the microparticle enzyme immunoassay.


RESULTS
Genistein, seleno-l-methionine and lycopene inhibited LNCaP cell growth, and the proliferation of C4-2 cells was suppressed by seleno-L-methionine and lycopene. PSA mRNA expression was downregulated by genistein in LNCaP but not C4-2 cells. No other compound tested altered PSA mRNA expression. PSA protein expression was downregulated by genistein, seleno-L-methionine, DL-alpha-tocopherol in LNCaP cells. In C4-2 cells only genistein significantly reduced the secretion of PSA protein.


CONCLUSIONS
In the LNCaP progression model PSA expression depends on the compound, its concentration and on the hormonal dependence of the cell line used and does not necessarily reflect cell growth or death. Before potential substances are evaluated in clinical trials using PSA as a surrogate end point marker, their effect on PSA mRNA and protein expression has to be considered to correctly assess treatment response by PSA.
Peternac
Daniel
D
Department of Urology, University of Bern, Bern, Switzerland.
Klima
Irena
I
Cecchini
Marco G
MG
Schwaninger
Ruth
R
Studer
Urs E
UE
Thalmann
George N
GN
D000230:Adenocarcinoma / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000378:metabolism; D002338:Carotenoids / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D019833:Genistein / Q000494:pharmacology; D006801:Humans; D000077276:Lycopene; D008297:Male; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control; D012333:RNA, Messenger / Q000378:metabolism; D012645:Selenomethionine / Q000494:pharmacology; D014815:Vitamins / Q000494:pharmacology; D024502:alpha-Tocopherol / Q000494:pharmacology; D019207:beta Carotene / Q000494:pharmacology
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D014815:Vitamins; D019207:beta Carotene; D002338:Carotenoids; D012645:Selenomethionine; D019833:Genistein; D017430:Prostate-Specific Antigen; D024502:alpha-Tocopherol; D000077276:Lycopene