PO-01-012 Tadalafil modulates aromatase and androgem receptor expression in human prostatic adenocarcinoma cells in vitro
Abstract
Our previous data suggest that Tadalafil (TAD), a phosphodiesterase type-5 inhibitor, has a direct effect on aromatase (ARO) expression and function in human visceral adipocytes; it also accelerates myogenic differentiation and induces higher expression of the androgen receptor (AR) in murine C2C12 muscle cells. In human osteoblastic cells in vitro, TAD modulates expression of ARO, and increases androgen receptor (AR) protein expression. We herein evaluated the potential modulation of ARO and sex steroid hormone receptors by TAD in prostate adenocarcinoma cells (LNCaP), a cellular in vitro model system of androgen-sensitive human adenocarcinoma. First series of experiments were performed to test LNCaP viability upon TAD exposure. Then, cells were treated with/without TAD 10-6M for several interval times to evaluate potential modulation of ARO, AR and estrogen receptor β (ERβ) expression. After 24 hs exposure to TAD, cells increases ARO mRNA expression level (p<0.05) and, as expected, an increase of ARO protein expression (p<0.01) after 48 hours occurred. Moreover, TAD exposure induced and increase of total AR protein expression (p<0.05) after 24 hours and there was an increased trend of ERβ mRNA expression level with maximal effects after 24 hours. Furthermore, there was an increased ratio of estradiol/testosterone levels in LNCaP in the supernatants, suggesting an increase in ARO activity after 48 hours.
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