Characteristics of the Biphasic Action of Androgens and of the Potent Antiproliferative Effects of the New Pure Antiestrogen EM-139 on Cell Cycle Kinetic Parameters in LNCaP Human Prostatic Cancer Cells
1991
Abstract The most potent steroid in human prostatic carcinoma LNCaP cells, i.e. , dihydrotestosterone (DHT), has a biphasic stimulatory effect on cell proliferation. At the maximal stimulatory concentration of 0.1 nm DHT, analysis of cell kinetic parameters shows a decrease of the G 0 -G 1 fraction with a corresponding increase of the S and G 2 + M fractions. In contrast, concentrations of 1 nm DHT or higher induce a return of cell proliferation to control levels, reflected by an increase in the G 0 -G 1 fraction at the expense of the S and especially the G 2 + M fractions. Continuous labeling for 144 h with the nucleotide analogue 5′-bromodeoxyuridine shows that the percentage of cycling LNCaP cells rises more than 90% after treatment with stimulatory concentrations of DHT, whereas in control cells as well as in cells treated with high concentrations of the androgen, this value remains below 50%. Although LNCaP cells do not contain detectable estrogen receptors, the new pure steroidal antiestrogen EM-139 not only reversed the stimulation of cell proliferation and cell kinetics induced by stimulatory doses of DHT but also inhibited basal cell proliferation.
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