Anti-tumour effect of aromatase inhibitor, CGS16949A, on human breast cancer cells.
The growth inhibitory effect of a new non-steroidal aromatase inhibitor, CGS16949A (Fadrozole hydrochloride: [4-(5,6,7,8-tetrahydro-imidazo-[1,5a]-pyridin-5-yl) benzonitrile monohydro chloride]) was studied in human breast cancer cells MCF-7 and T47D. The aromatase activity of MCF-7 was inhibited by CGS16949A in a dose-dependent manner (IC50: 2.8 x 10(-9) M). The cells were incubated for 120 h in phenol red free RPMI 1640 containing 5% stripped foetal calf serum, 10(-8) M testosterone and various concentrations of CGS16949A. Testosterone-induced MCF-7 growth was inhibited by CGS16949A almost completely at the concentrations as low as 10(-9) M, but was not inhibited by antiandrogenic cyproterone acetate (6-chloro-1 beta,2 beta-dihydro-17-hydroxy-3'-H- cyclopropa[1,2]-pregna-1,4,6-triene-3,20-dione acetate: CPA). On the other hand, the growth of T47D stimulated by testosterone was not inhibited by CGS16949A, but was inhibited by CPA. These data suggested that the aromatization of androgens should participate in the growth of MCF-7 and that one of the growth inhibitory mechanisms of CGS16949A should be the inhibition of the intracellular aromatase activity.
Yano
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S
Drug Discovery Research Unit, Ciba-Geigy Japan Limited 10-66, Takarazuka, Japan.
Tanaka
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M
Nakao
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D001141:Aromatase / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D017316:Fadrozole / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D013739:Testosterone / Q000494:pharmacology; D013997:Time Factors; D014407:Tumor Cells, Cultured
D013739:Testosterone; D001141:Aromatase; D017316:Fadrozole