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 / Bimonte, V. M.; Marampon, F.; Antonioni, A.; Fittipaldi, S.; Ferretti, E.; Pestell, R. G.; Curreli, M.; Lenzi, A.; Vitale, G.; Brunetti, A.; Migliaccio, S.; Aversa, A.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:2(2021). [10.3390/ijms22020754]

Phosphodiesterase type-5 inhibitor tadalafil modulates steroid hormones signaling in a prostate cancer cell line

Bimonte V. M.
Primo
;
Marampon F.
Secondo
;
Antonioni A.;Fittipaldi S.;Ferretti E.;Curreli M.;Lenzi A.;Migliaccio S.
Penultimo
;
2021

Abstract

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.
2021
androgen resistance; aromatase; bicalutamide; prostate cancer; tadalafil
01 Pubblicazione su rivista::01a Articolo in rivista
Phosphodiesterase type-5 inhibitor tadalafil modulates steroid hormones signaling in a prostate cancer cell line / Bimonte, V. M.; Marampon, F.; Antonioni, A.; Fittipaldi, S.; Ferretti, E.; Pestell, R. G.; Curreli, M.; Lenzi, A.; Vitale, G.; Brunetti, A.; Migliaccio, S.; Aversa, A.. - In: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES. - ISSN 1661-6596. - 22:2(2021). [10.3390/ijms22020754]
File allegati a questo prodotto
File Dimensione Formato  
Bimonte_Phosphodiesterase Type-5_2021.pdf

accesso aperto

Note: https://www.mdpi.com/1422-0067/22/2/754
Tipologia: Versione editoriale (versione pubblicata con il layout dell'editore)
Licenza: Creative commons
Dimensione 1.38 MB
Formato Adobe PDF
1.38 MB Adobe PDF

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1521530
Citazioni
  • ???jsp.display-item.citation.pmc??? 3
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 6
social impact