Anti-proliferative effects of 1,2-diphenylethane oestrogens and anti-oestrogens on human breast cancer cells.
The anti-tumour activities of 1,2-diphenylethane oestrogens (hexoestrol and orthohexoestrol) and anti-oestrogens (metahexoestrol, tetramethylHES, and metatetramethylHES) were studied on the human MCF-7 and MDA-MB-231 breast cancer cell lines. On the E2R-positive MCF-7 cell line, all test compounds exhibited a dose-dependent inhibition of cell proliferation, but no correlation between anti-proliferative activity and binding affinity for the E2R was found. Tested on the E2R-negative MDA-MB-231 cell line, metahexoestrol also showed dose-dependent inhibitory effects, but higher concentrations were necessary than on the MCF-7 cell line. From this it is concluded that the anti-proliferative effect is specific and at least partially mediated via the E2R. Combination of metahexoestrol (10(-6)M) with E2 (10(-9) to 10(-7)M) gave no rescue effect. It is therefore suggested that this compound might be useful for therapy in the presence of high oestrogen levels, i.e. in pre-menopausal patients. The test compounds (10(-8) to 10(-6)M) could rescue the inhibitory effect of tamoxifen (10(-6)M) in a dose-dependent manner, except in the cases of metahexoestrol (10(-6)M) and tetramethylHES (10(-6)M). The latter compound exhibited a strongly additive effect at this concentration.
Hartmann
R W
RW
Sinchai
T
T
Kranzfelder
G
G
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004965:Estrogen Antagonists / Q000494:pharmacology*; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D006589:Hexestrol / Q000031:analogs & derivatives* / Q000494:pharmacology; D006801:Humans; D011959:Receptors, Estradiol / Q000378:metabolism
D004965:Estrogen Antagonists; D004967:Estrogens; D011959:Receptors, Estradiol; D006589:Hexestrol