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Open AccessArticle

Phosphodiesterase Type-5 Inhibitor Tadalafil Modulates Steroid Hormones Signaling in a Prostate Cancer Cell Line

Department of Movement, Human and Health Sciences, “Foro Italico” University, 00135 Rome, Italy
Department of Experimental Medicine, “Sapienza” University of Rome, 00161 Rome, Italy
Department of Experimental and Clinical Medicine, Magna Græcia University, 88100 Catanzaro, Italy
Department of Radiological, Oncological and Pathological Sciences, “Sapienza” University, 00161 Rome, Italy
Department of Biomedicine and Prevention, “Tor Vergata” University, 00133 Rome, Italy
Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg Institute, Pennsylvania Biotechnology Center, Wynnewood, PA 19111, USA
Department of Medical Biotechnologies and Translational Medicine, University of Milan, 20122 Milan, Italy
Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto Auxologico Italiano, IRCCS, Cusano Milanino, 20095 Milan, Italy
Department of Health Sciences, Magna Graecia University, 88100 Catanzaro, Italy
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2021, 22(2), 754;
Received: 15 December 2020 / Revised: 7 January 2021 / Accepted: 8 January 2021 / Published: 13 January 2021
(This article belongs to the Special Issue Molecular Biomarkers in Cancer and Metabolic Disease)
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. View Full-Text
Keywords: tadalafil; prostate cancer; androgen resistance; aromatase; bicalutamide tadalafil; prostate cancer; androgen resistance; aromatase; bicalutamide
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MDPI and ACS Style

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. Phosphodiesterase Type-5 Inhibitor Tadalafil Modulates Steroid Hormones Signaling in a Prostate Cancer Cell Line. Int. J. Mol. Sci. 2021, 22, 754.

AMA Style

Bimonte VM, Marampon F, Antonioni A, Fittipaldi S, Ferretti E, Pestell RG, Curreli M, Lenzi A, Vitale G, Brunetti A, Migliaccio S, Aversa A. Phosphodiesterase Type-5 Inhibitor Tadalafil Modulates Steroid Hormones Signaling in a Prostate Cancer Cell Line. International Journal of Molecular Sciences. 2021; 22(2):754.

Chicago/Turabian Style

Bimonte, Viviana M.; Marampon, Francesco; Antonioni, Ambra; Fittipaldi, Simona; Ferretti, Elisabetta; Pestell, Richard G.; Curreli, Mariaignazia; Lenzi, Andrea; Vitale, Giovanni; Brunetti, Antonio; Migliaccio, Silvia; Aversa, Antonio. 2021. "Phosphodiesterase Type-5 Inhibitor Tadalafil Modulates Steroid Hormones Signaling in a Prostate Cancer Cell Line" Int. J. Mol. Sci. 22, no. 2: 754.

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