Stimulatory effect of synthetic progestins currently used for the treatment of prostate cancer on growth of the androgen-sensitive Shionogi tumor in mice.
In order to assess the androgenic activity of synthetic progestins currently used as "antiandrogens" for the treatment of prostate cancer in men, the effect of a series of these compounds has been studied in mice on the growth of the androgen-sensitive Shionogi tumor. Female mice (DD/S strain) were inoculated subcutaneously with 10(6) viable cells and divided into groups who received, respectively, the synthetic "progestins" medroxyprogesterone acetate (MPA), megestrol acetate (MEG), cyproterone acetate (CPA) or chlormadinone acetate (CMA), compared with the non-steroidal antiandrogen Flutamide (Flu), each administered at the twice-daily dose of 250 micrograms. Each synthetic "progestin" exerted a marked stimulatory effect on the growth of the tumor. The most impressive effect on growth was observed with MPA. In fact, in MPA-treated mice, tumor size was 17 times larger than control at 4.92 +/- 0.36 cm2/mouse 21 days after inoculation. CPA, CMA and MEG also stimulated the growth of this androgen-sensitive tumor, the percentages of stimulation of tumor size being 3.1-, 3.2- and 11.0-fold above control, respectively, on day 21, while Flu had no significant stimulatory effect. The present data clearly show that all the above-mentioned progestins have variable levels of stimulatory activity on the growth of the androgen-sensitive Shionogi tumor and indicate that such drugs are unlikely to be recommendable for the treatment of prostate cancer.
Plante
M
M
Medical Research Council Group in Molecular Endocrinology, Laval University Medical Center, Quebec, Canada.
Lapointe
S
S
Labrie
F
F
D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D002715:Chlormadinone Acetate / Q000627:therapeutic use; D003534:Cyproterone / Q000031:analogs & derivatives / Q000627:therapeutic use; D017373:Cyproterone Acetate; D005260:Female; D005485:Flutamide / Q000627:therapeutic use; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy; D008525:Medroxyprogesterone / Q000031:analogs & derivatives / Q000627:therapeutic use; D017258:Medroxyprogesterone Acetate; D008535:Megestrol / Q000031:analogs & derivatives / Q000627:therapeutic use; D019290:Megestrol Acetate; D051379:Mice; D045167:Progesterone Congeners / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*
D000728:Androgens; D045167:Progesterone Congeners; D002715:Chlormadinone Acetate; D017373:Cyproterone Acetate; D005485:Flutamide; D017258:Medroxyprogesterone Acetate; D003534:Cyproterone; D008535:Megestrol; D008525:Medroxyprogesterone; D019290:Megestrol Acetate