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.

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 G0-G1 fraction with a corresponding increase of the S and G2 + 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 G0-G1 fraction at the expense of the S and especially the G2 + 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.

• Authors: Y de Launoit, R Veilleux, M Dufour, J Simard, F Labrie
• Journal: Cancer research (Cancer Res) Vol. 51 Issue 19 Pg. 5165-70 (Oct 01 1991) ISSN: 0008-5472 [Print] United States
• PMID: 1913642 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Androgens
• Estrogen Antagonists
• Piperidines
• Dihydrotestosterone
• Tamoxifen
• EM 139
• Androstane-3,17-diol
• Metribolone
• Estrone
• hydroxyflutamide
• Testosterone
• Raloxifene Hydrochloride
• Estradiol
• Flutamide

Topics

• Androgens (pharmacology)
• Androstane-3,17-diol (pharmacology)
• Binding, Competitive
• Cell Cycle (drug effects)
• Dihydrotestosterone (pharmacology)
• Dose-Response Relationship, Drug
• Drug Antagonism
• Estradiol (analogs & derivatives, pharmacology)
• Estrogen Antagonists (pharmacology)
• Estrone (pharmacology)
• Flow Cytometry
• Flutamide (analogs & derivatives, pharmacology)
• Humans
• In Vitro Techniques
• Male
• Metribolone (metabolism)
• Piperidines (pharmacology)
• Prostatic Neoplasms (drug therapy, pathology)
• Raloxifene Hydrochloride
• Tamoxifen (analogs & derivatives)
• Testosterone (metabolism)
• Time Factors
• Tumor Cells, Cultured