Background: The androgen receptor (AR) plays a key role in normal prostate homeostasis and in prostate cancer (PCa) development, while the role of aromatase (Cyp19a1) is still unclear. We evaluated the effects of a treatment with Tadalafil (TAD) on both these proteins. Methods: Androgen-sensitive human PCa cell line (LnCAP) was incubated with/without TAD (10−6 M) and bicalutamide (BCT) (10−4 M) to evaluate a potential modulation on cell proliferation, protein and mRNA expression of Cyp19a, AR and estrogen receptor-β (ERβ), respectively. Results: TAD increased early AR nuclear translocation (p < 0.05, after 15 min of exposure), and increased AR transcriptional activity (p < 0.05) and protein expression (p < 0.05) after 24 h. Moreover, after 24 h this treatment upregulated Cyp19a1 and ERβ mRNA (p < 0.05 and p < 0.005 respectively) and led to an increase in protein expression of both after 48 h (p < 0.05). Interestingly, TAD counteracted Cyp19a1 stimulation induced by BCT (p < 0.05) but did not alter the effect induced by BCT on the AR protein expression. Conclusion: We demonstrate for the first time that TAD can significantly modulate AR expression and activity, Cyp19a1 and ERβ expression in PCa cells, suggesting a specific effect of these proteins. In addition, TAD potentiates the antiproliferative activity of BCT, opening a new clinical scenario in the treatment of PCa.
Phosphodiesterase type-5 inhibitor tadalafil modulates steroid hormones signaling in a prostate cancer cell line / V.M. Bimonte, F. Marampon, A. Antonioni, S. Fittipaldi, E. Ferretti, R.G. Pestell, M. Curreli, A. Lenzi, G. Vitale, A. Brunetti, S. Migliaccio, A. Aversa. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:2(2021), pp. 754.1-754.15.
|Titolo:||Phosphodiesterase type-5 inhibitor tadalafil modulates steroid hormones signaling in a prostate cancer cell line|
|Parole Chiave:||tadalafil; prostate cancer; androgen resistance; aromatase; bicalutamide|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
|Data di pubblicazione:||2021|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.3390/ijms22020754|
|Appare nelle tipologie:||01 - Articolo su periodico|