PMID- 33451122
OWN - NLM
STAT- MEDLINE
DCOM- 20210407
LR  - 20210407
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 22
IP  - 2
DP  - 2021 Jan 13
TI  - Phosphodiesterase Type-5 Inhibitor Tadalafil Modulates Steroid Hormones Signaling 
      in a Prostate Cancer Cell Line.
LID - 10.3390/ijms22020754 [doi]
LID - 754
AB  - 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-beta (ERbeta), 
      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 ERbeta 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 ERbeta 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.
FAU - Bimonte, Viviana M
AU  - Bimonte VM
AD  - Department of Movement, Human and Health Sciences, "Foro Italico" University, 
      00135 Rome, Italy.
AD  - Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, 
      Italy.
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 
      Catanzaro, Italy.
FAU - Marampon, Francesco
AU  - Marampon F
AD  - Department of Radiological, Oncological and Pathological Sciences, "Sapienza" 
      University, 00161 Rome, Italy.
FAU - Antonioni, Ambra
AU  - Antonioni A
AD  - Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, 
      Italy.
FAU - Fittipaldi, Simona
AU  - Fittipaldi S
AUID- ORCID: 0000-0001-7578-395X
AD  - Department of Biomedicine and Prevention, "Tor Vergata" University, 00133 Rome, 
      Italy.
FAU - Ferretti, Elisabetta
AU  - Ferretti E
AUID- ORCID: 0000-0001-7265-6429
AD  - Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, 
      Italy.
FAU - Pestell, Richard G
AU  - Pestell RG
AUID- ORCID: 0000-0003-3244-8777
AD  - Pennsylvania Cancer and Regenerative Medicine Research Center, Baruch S. Blumberg 
      Institute, Pennsylvania Biotechnology Center, Wynnewood, PA 19111, USA.
FAU - Curreli, Mariaignazia
AU  - Curreli M
AD  - Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, 
      Italy.
FAU - Lenzi, Andrea
AU  - Lenzi A
AD  - Department of Experimental Medicine, "Sapienza" University of Rome, 00161 Rome, 
      Italy.
FAU - Vitale, Giovanni
AU  - Vitale G
AUID- ORCID: 0000-0003-2478-683X
AD  - Department of Medical Biotechnologies and Translational Medicine, University of 
      Milan, 20122 Milan, Italy.
AD  - Laboratory of Geriatric and Oncologic Neuroendocrinology Research, Istituto 
      Auxologico Italiano, IRCCS, Cusano Milanino, 20095 Milan, Italy.
FAU - Brunetti, Antonio
AU  - Brunetti A
AUID- ORCID: 0000-0003-1533-8779
AD  - Department of Health Sciences, Magna Graecia University, 88100 Catanzaro, Italy.
FAU - Migliaccio, Silvia
AU  - Migliaccio S
AUID- ORCID: 0000-0002-4563-6630
AD  - Department of Movement, Human and Health Sciences, "Foro Italico" University, 
      00135 Rome, Italy.
FAU - Aversa, Antonio
AU  - Aversa A
AUID- ORCID: 0000-0002-2989-2618
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 88100 
      Catanzaro, Italy.
LA  - eng
GR  - 2015XCR88M_008/Agenzia Italiana del Farmaco, Ministero della Salute/
GR  - 2017HBHA98/Agenzia Italiana del Farmaco, Ministero della Salute/
PT  - Journal Article
DEP - 20210113
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (AR protein, human)
RN  - 0 (Biomarkers)
RN  - 0 (Hormones)
RN  - 0 (Phosphodiesterase 5 Inhibitors)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Steroids)
RN  - 742SXX0ICT (Tadalafil)
SB  - IM
MH  - Biomarkers
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Drug Resistance, Neoplasm
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation, Neoplastic
MH  - Hormones/*metabolism
MH  - Humans
MH  - Male
MH  - Phosphodiesterase 5 Inhibitors/*pharmacology
MH  - Prostatic Neoplasms/drug therapy/etiology/*metabolism/pathology
MH  - Protein Transport
MH  - Receptors, Androgen/genetics/metabolism
MH  - Signal Transduction/*drug effects
MH  - Steroids/*metabolism
MH  - Tadalafil/*pharmacology
PMC - PMC7828628
OTO - NOTNLM
OT  - androgen resistance
OT  - aromatase
OT  - bicalutamide
OT  - prostate cancer
OT  - tadalafil
COIS- The authors declare no conflict of interest.
EDAT- 2021/01/17 06:00
MHDA- 2021/04/10 06:00
PMCR- 2021/01/13
CRDT- 2021/01/16 01:02
PHST- 2020/12/15 00:00 [received]
PHST- 2021/01/07 00:00 [revised]
PHST- 2021/01/08 00:00 [accepted]
PHST- 2021/01/16 01:02 [entrez]
PHST- 2021/01/17 06:00 [pubmed]
PHST- 2021/04/10 06:00 [medline]
PHST- 2021/01/13 00:00 [pmc-release]
AID - ijms22020754 [pii]
AID - ijms-22-00754 [pii]
AID - 10.3390/ijms22020754 [doi]
PST - epublish
SO  - Int J Mol Sci. 2021 Jan 13;22(2):754. doi: 10.3390/ijms22020754.