EFFECT OF PROMEGESTONE, TAMOXIFEN, 4-HYDROXYTAMOXIFEN AND ICI 164,384ON THE ESTRONE SULFATASE ACTIVITY OF HUMAN BREAST-CANCER CELLS

In the present study, we explored the effects on sulphatase activity b y Promegestone (R-5020), Tamoxifen (TAM), 4-hydroxytamoxifen (4-OH-TAM ) and ICI 164,384 in the T-47D hormone-dependent and MDA-MB-231 hormon e-independent mammary cancer cell lines. Using homogenates of these ce lls it was observed that Promegestone has a significant effect on the inhibition of oestrone (E1) sulphatase activity. As this effect is com petitive, it is suggested that there is a direct action of this compou nd on the enzyme. Tamoxifen has very little or no effect, 4-hydroxytam oxifen has an intermediate effect and ICI 164,384 is active in the enz yme inhibition, particularly with MDA-MB-231 cells. The present data c ould open new possibilities for human breast cancer treatment, as sulp hatase is very active in the first step of the conversion of oestrone sulphate (E1S) to oestradiol (E2), and oestradiol is one of the princi pal carcinogenic factors in human hormone-dependent breast cancer.