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Responses of LNCaP prostatic adenocarcinoma cell cultures to LY300502, a benzoquinolinone human type I 5α‐reductase inhibitor
Author(s) -
Sutkowski Debra M.,
Audia James E.,
Goode Robin L.,
Hsiao Kenneth C.,
Leibovitch Ilan Y.,
McNulty Ann M.,
Neubauer Blake Lee
Publication year - 1996
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(1996)6+<62::aid-pros12>3.0.co;2-p
Subject(s) - lncap , endocrinology , medicine , androgen , cell growth , biology , cancer cell , cancer , biochemistry , hormone
We evaluated the metabolic inhibitory, antiproliferative, and antisecretory effects of LY300502, a benzoquinolinone human‐specific type I‐selective steroid 5α‐reductase inhibitor in LNCaP human prostatic adenocarcinoma cell cultures. Reductive metabolism of [ 3 H‐T] in the LNCaP cells was inhibited in a concentration‐dependent manner by LY300502 (IC 50 ≃ 5.77 nM). The proliferative responses of LNCaP cells to LY300502 were examined in the presence of 0.1 nM testosterone (T), a concentration that stimulates maximal LNCaP cellular proliferation. Addition of 0.1 nM T to the culture media significantly stimulated LNCaP cell numbers 40% above control levels. LY300502 significantly antagonized T‐induced stimulation of LNCaP cellular proliferation at concentrations greater than 10 nM ( P < 0.05), and at 1,000 nM completely blocked the mitogenic effects of T on LNCaP cells. In the absence of androgen, LY300502 had no effect on LNCaP cellular proliferation. In the presence of 100 nM T, an androgen concentration that maximally stimulates in vitro PSA production, LY300502 significantly antagonized T‐induced PSA secretion at a concentration equal to or greater than 30 nM ( P < 0.05). These studies provide the basis for additional investigations into the pathophysiologic significance of type I 5α‐reductase to prostatic cancer and the potential utility of selective inhibitors as therapeutic agents. © 1996 Wiley‐Liss, Inc.