Oestrogen sulphatase activity in hormone-dependent and hormone-independent breast-cancer cells: modulation by steroidal and non-steroidal therapeutic agents.
Oestrogen sulphatase may play an important role in providing intracellular oestrogens from E1S for the growth and maintenance of breast tumours. In this study, we characterized oestrogen sulphatase in the hormone-dependent (ER/PR+) MCF-7 and in the hormone-independent (ER/PR-) MDA-MB-231 breast-cancer cells and, furthermore, examined its modulation by MPA, 4-OH-A4, tamoxifen, danazol, ethinyloestradiol and DHAS in both these cell types. Our detailed study of oestrogen sulphatase activity as a function of incubation time, E1S concentration and numbers of MCF-7 and MDA-MB-231 cells showed that more E1S was hydrolysed by MDA-MB-231 cells than by MCF-7 cells at all time points and all substrate concentrations. Additionally, although the Km values of E1S for oestrogen sulphatase in both MCF-7 and MDA-MB-231 cells were similar, the Vmax values, and therefore the activity, differed greatly. The effect of various steroidal and non-steroidal compounds also suggested differences in these 2 cell lines with respect to oestrogen sulphatase inhibition or stimulation. MPA significantly increased the hydrolysis of [3H]E1S in both cell lines, possibly through its effect on membrane fluidity. Tamoxifen increased E1S hydrolysis in MDA-MB-231 cells but not in MCF-7 cells, whereas 4-OH-A4 inhibited E1S in MCF-7 cells but not in MDA-MB-231 cells. Danazol (an isoxazol derivative of 17 alpha-ethinyltestosterone), 17 alpha-ethinyloestradiol and DHAS all significantly inhibited oestrogen sulphatase activity in both cell lines. Furthermore, danazol had a growth-inhibitory effect on both MCF-7 and MDA-MB-231 cells, although MCF-7 cells appeared to be more sensitive to growth inhibition by danazol.
Purohit
A
A
Department of Chemical Pathology, St. Mary's Hospital Medical School, Imperial College of Science, Technology and Medicine, University of London, UK.
Reed
M J
MJ
D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D003613:Danazol / Q000494:pharmacology*; D003687:Dehydroepiandrosterone / Q000031:analogs & derivatives* / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate; D004997:Ethinyl Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013429:Sulfatases / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013629:Tamoxifen; D004997:Ethinyl Estradiol; D003687:Dehydroepiandrosterone; D019314:Dehydroepiandrosterone Sulfate; D013429:Sulfatases; C039596:estrogen sulfatase; D003613:Danazol