Effects of simvastatin, acetylsalicylic acid, and rosiglitazone on proliferation of normal and cancerous prostate epithelial cells at therapeutic concentrations.
BACKGROUND
Non-steroidal anti-inflammatory drugs and cholesterol-lowering statins have been reported to inhibit prostate cancer cell growth suggesting their chemopreventive potential within the prostate. However, the effect has been demonstrated only with advanced prostate cancer cell lines and with drug concentrations above the clinical therapeutic range. In this study we compared the effect of therapeutic concentrations of acetylsalicylic acid, simvastatin and rosiglitazone on the growth of a set of prostatic primary cultures and various prostate epithelial cell lines.


METHODS
Two primary epithelial cell lines isolated from surgical resecates of normal prostate tissue (P96E, P97E), a primary cell line isolated from untreated prostate carcinoma (ESTO1), two transformed prostate epithelial cell lines (PWR1-E, RWPE-1) and advanced cancer cell lines LNCaP and VCaP were used in the study. Cells were treated for seven days with therapeutic concentrations of acetylsalisylic acid, simvastatin, rosiglitazone or their combination. Cellular growth rate was measured by crystal violet staining method.


RESULTS
Acetylsalicylic acid (0.5 mM) and simvastatin (10 nM) inhibited the growth of prostate epithelial cells of normal and primary cancer origin, whereas advanced cancer cell lines were resistant to the effect. Rosiglitazone at the therapeutic level of 1 microM did not reduce the growth of any cell type studied.


CONCLUSIONS
Our results demonstrate that acetylsalicylic acid and simvastatin inhibit prostate epithelial cell growth at clinically relevant doses. This should be acknowledged when designing possible prostate cancer chemopreventive trials.
Murtola
Teemu J
TJ
School of Public Health, University of Tampere, Tampere, Finland. teemu.murtola@uta.fi
Pennanen
Pasi
P
Syvälä
Heimo
H
Bläuer
Merja
M
Ylikomi
Timo
T
Tammela
Teuvo L J
TL
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects*; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D008297:Male; D011467:Prostate / Q000473:pathology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D000077154:Rosiglitazone; D019821:Simvastatin / Q000494:pharmacology*; D045162:Thiazolidinediones / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006131:Growth Inhibitors; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D019821:Simvastatin; D001241:Aspirin