Reference

Comparative studies of 5a-reductase inhibitors within MCF-7 human breast cancer cells

Comparative studies of 5a-reductase inhibitors within MCF-7 human breast cancer cells. MacIndoe, John H.; West, E. R.; Petrow, Vladimir (Dep. Intern. Med., Veterans Adm. Med. Cent., Iowa City, IA 52240, USA). J. Steroid Biochem., 20(5), 1095-100 (English) 1984. CODEN: JSTBBK. ISSN: 0022-4731. DOCUMENT TYPE: Journal CA Section: 2 (Mammalian Hormones) The inhibitory effects of 6 synthetic steroid analogs (17b-carboxy-4-androsten-3-one benzylamide (VP-1)(I) [91203-71-3], 17a-acetoxy-6-methylene-4-pregnene-3,20-dione (VP-2) [32634-95-0], 6-methylene-4-pregnene-3,20-dione (VP-3) [19457-57-9], 17b-acetoxy-6-methylene-4-androsten-3-one (VP-4) [1100-17-0], 17b-acetoxy-16,16-dimethyl-6-methylen-4-androsten-3-one (VP-5) [91203-70-2], and 3b-hydroxy-16-methylen-5-androsten-17-one (VP-6) [2862-67-1] on 5a-reductase [9036-43-5] activity were compared within MCF-7 human breast cancer cells and rat prostate. At 5 mM, VP-2 and VP-3 inhibited prostatic 5a-reductase by 55% and 65%, resp., whereas the other analogs showed little activity. In contrast, each of the 6 analogs was active against MCF-7 homogenate 5a-reductase activity. VP-2 and VP-4 demonstrated approx. 65% and 70% inhibitions, resp., whereas the other 4 compds. inhibited enzyme activity by 40-55% in this system. Rat prostate and MCF-7 cells apparently contain different 5a-reductase isozymes. When these agents were examd. for 5a-reductase inhibitory activity following 1 h preincubations with intact MCF-7 cultures, VP-1 and VP-3 demonstrated potencies similar to those in MCF-7 homogenate. The other compds., however, were far less active under these conditions. Longer culture preincubation (16 h) were assocd. with substantially increased VP-6 potency, moderate increases for VP-4 and VP-5, and no change in VP-2 activity. Studies of the abilities of these agents to bind to MCF-7 androgen receptor (AR) and progesterone (PR) revealed moderate AR binding activities of VP-2, VP-3, and VP-4, and substantial PR binding for VP-2 and VP-3. VP-4 failed to inhibit estrogen-dependent MCF-7 PR synthesis, suggesting that it has no androgenic activity despite its ability to interact with MCF-7 AR.

Spectrophotometric analysis

Spectrophotometric analysis. 11. Analysis of mixtures of steroid dienones by the circular dichroism method. Potapov, V. M.; Dem'yanovich, V. M.; Rakovska, R. S.; Grinenko, G. S.; Kadatskii, G. M. (Moscow State Univ., Moscow, USSR). Zh. Anal. Khim., 33(3), 534-7 (Russian) 1978. CODEN: ZAKHA8. ISSN: 0044-4502. DOCUMENT TYPE: Journal CA Section: 64 (Pharmaceutical Analysis) Anal. of a mixt. of steroid dienones I [32634-95-0] and II [595-33-5] depended on the differences in their CD curves. The control of I to II isomerization was based on their optical notations (Q) at 292 nm at which [Q]292 for II and I are 0° and 21,000°, resp. Difference in optical rotations at 238 nm ([Q]238 = 0° and 17,000° for I and II, resp.) may be used to check the purity of the end product II. Also, noticeable differences are found at other wavelengths.