Anti-proliferative effect of a triazole derivative (ST1959) on LNCaP human prostate cancer cells through down-regulation of cyclin and androgen receptor expression.
BACKGROUND
Previous studies demonstrated that ST1959, a triazole derivative endowed with immunomodulatory activities, also exerts inhibitory effects on proliferation and survival of a panel of tumor cells. In this study, we sought to ascertain the effects of ST1959 on the growth of androgen-dependent and androgen-independent prostate cancer (PCa) cells.


METHODS
The growth of androgen-dependent (LNCaP) and androgen-independent (PC3, DU-145) cells was analyzed in vitro both in the presence and absence of ST1959. Modulation of cyclin and androgen receptor (AR) expression following treatment with ST1959 was analyzed by Western blot and cytofluorimetric analysis.


RESULTS
We observed that ST1959 causes a significant growth inhibition of LNCaP cells without affecting proliferation of androgen-insensitive DU-145 and PC3 cell lines. These effects were associated with G0/G1 cell cycle arrest and down-regulation of cyclin D1, A and B and AR expression.


CONCLUSIONS
Our present findings indicate that the anti-proliferative activity of ST1959 on cell growth of androgen-dependent LNCaP PCa cells may be brought about by decreasing expression of functional AR and selected cyclins, ultimately leading to cell growth inhibition.
Loiarro
Maria
M
Department of Public Health and Cell Biology, University of Rome Tor Vergata, Rome, Italy.
Campo
Silvia
S
Arseni
Brunilde
B
Rossi
Stefania
S
D'Alessio
Valeria
V
De Santis
Rita
R
Sette
Claudio
C
Ruggiero
Vito
V
D000230:Adenocarcinoma / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D016213:Cyclins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011944:Receptors, Androgen / Q000378:metabolism*; D014230:Triazoles / Q000494:pharmacology*
D016213:Cyclins; D007166:Immunosuppressive Agents; D011944:Receptors, Androgen; D014230:Triazoles; C030266:3-(2-ethylphenyl)-5-(3-methoxyphenyl)-1H-1,2,4-triazole