ABSTRACT
Antitumor activity of a new highly active promising gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one (butagest) was studied in mice with model cervical carcinoma (RShM-5). The reference drug was medroxyprogesteron acetate (MPA, Depo Provera) used in clinics. The new preparation introduced perorally in a dose of 1 mg per mice inhibited the model tumor growth by 73%, which was 18% (p < 0.01) more effective than the action of the reference drug MPA. The effect of the new gestagen was also studied in vitro with respect to human breast carcinoma of the MCF-7 line and human cervical carcinoma HeLa. The viability of the tumor cells was studied during a 6-day incubation with the drug at a concentration of 10(-7)-10(-5) M (MTT test). The reference compounds were progesterone and MPA. These drugs suppressed the growth of both MCF-7 and, in higher concentrations, of HeLa. Butagest inhibited the growth of HeLa in all concentrations. Thus, the new gestagen 17alpha-acetoxy-3beta-butanoyloxy-6-methyl-pregna-4,6-dien-20-one is capable of suppressing the viability of human breast carcinoma and human cervical carcinoma, being comparable or even more effective than the reference drugs.
Subject(s)
17-alpha-Hydroxyprogesterone/analogs & derivatives , 17-alpha-Hydroxyprogesterone/therapeutic use , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Carcinoma/drug therapy , Uterine Cervical Neoplasms/drug therapy , 17-alpha-Hydroxyprogesterone/pharmacology , Animals , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Female , Humans , Medroxyprogesterone Acetate/pharmacology , Medroxyprogesterone Acetate/therapeutic use , Mice , Mice, Inbred CBA , Progestins/pharmacology , Progestins/therapeutic useABSTRACT
Temporal and concentration dependencies of the effects of gestagens (6alpha-methylpentarane and progesterone) and cytostatic doxorubicin on proliferation of MCF-7 and HeLa tumor cells was studied using(3)H-thymidine test. Gestagens produced the maximum inhibitory effect of on cell proliferation in a concentration of 10(-5)M; the effect developed on day 6 of incubation. 6 alpha-Methylpentarane in a concentration of 10(-8)inhibited proliferation of HeLa cells more effectively than progesterone (p<0.05). In experiments with combined treatment of doxorubicin-sensitive MCF-7 and HeLa cells, progesterone in a concentration of 10(-7)M attenuated the cytostatic effect of doxorubicin (p<0.05), while 6alpha-methylpentarane in the studied concentrations did not modulate it.
