Melengestrol acetate and megestrol acetate are prostatic tumor inhibiting agents.

Abstract

We had previously reported that 6-methylene progesterone, an inhibitor of 5 alpha-reductase, the enzyme which converts testosterone to dihydrotestosterone, markedly inhibited growth of the androgen-dependent Dunning R3327-H rat prostatic tumors. We now find that the progesterone derivatives melengestrol acetate (MGA) and megestrol acetate (MA) inhibit both the androgen-dependent (Dunning R3327-H) and the androgen-independent (Dunning R3327-AT3) prostatic tumors. Growth of the AT3 tumors was suppressed by approximately 53% after 9 days of daily s.c. injections with MGA at 10 mg/kg body weight. MGA also caused a 54% weight reduction of the ventral prostate and a 53% reduction of the seminal vesicles. Adrenal weights were reduced by 42%. A 24-day oral treatment with MGA (at approximately 15-17 mg/(kg.day)) inhibited AT3 tumor growth by 59% and caused a weight reduction in the following tissues: prostate (46%), seminal vesicles (19%), testes (12%), and adrenals (52%). Under the same protocol, MA inhibited AT3 tumor growth by 32% and reduced the weight of the ventral prostate by 49% and the weight of the adrenals by 18%, but had no effect on the seminal vesicles and testes. The extent of the MGA-induced prostatic regression was accompanied by cytological changes similar to those effected by 6-methylene progesterone, i.e., shrinking of the acinar epithelium. The AT3 tumors in MGA-treated rats displayed a limited degree of apoptosis. Atrophy of the adrenal cortex and lowered plasma levels of corticosterone and dihydroepiandrosterone were also observed. A therapeutic role for MGA and MA against androgen-independent prostatic neoplasms in man is forecast by these observations.

• Authors: G M Padilla, R C Yacullo, J J Padilla, B Payne, V Petrow
• Journal: Biochemistry and cell biology = Biochimie et biologie cellulaire (Biochem Cell Biol) Vol. 68 Issue 10 Pg. 1181-8 (Oct 1990) ISSN: 0829-8211 [Print] Canada
• PMID: 2268413 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Melengestrol Acetate
• Megestrol
• Megestrol Acetate

Topics

• Adrenal Glands (drug effects, pathology)
• Animals
• Antineoplastic Agents
• Dose-Response Relationship, Drug
• Male
• Megestrol (analogs & derivatives, pharmacology)
• Megestrol Acetate
• Melengestrol Acetate (pharmacology)
• Neoplasms, Hormone-Dependent (drug therapy, pathology)
• Prostate (drug effects, pathology)
• Prostatic Neoplasms (drug therapy, pathology)
• Rats
• Rats, Inbred Strains
• Seminal Vesicles (drug effects, pathology)