Control of sulfatase and sulfotransferase activities by medrogestone in the hormone-dependent MCF-7 and T-47D human breast cancer cell lines.
In the present study, we explored the effect of the progestin medrogestone on the sulfatase and sulfotransferase activities in the hormone-dependent MCF-7 and T-47D human breast cancer cell lines. After 24 h incubation at 37 degrees C of physiological concentrations of estrone sulfate ([3H]-E1S: 5x10(-9) mol/l), it was observed that this estrogen was converted in a great proportion to E2 in both cell lines. Medrogestone significantly inhibits this transformation, at all the concentrations tested (5x10(-8) to 5x10(-5) mol/l), in both cell lines. The IC50 values were 1.93 micromol/l and 0.21 micromol/l in MCF-7 and T-47D cells, respectively. In another series of studies, after 24 h incubation at 37 degrees C of physiological concentrations of estrone ([3H]-E1: 5x10(-9) mol/l), the sulfotransferase activity was detectable in both cell lines. Estrogen sulfates (ES) are found exclusively in the culture medium, which suggests that as soon as they are formed they are excreted into the medium. Medrogestone has a biphasic effect on sulfotransferase activity in both cell lines. At low doses: 5x10(-8) and 5x10(-7) mol/l, this compound stimulates the enzyme by +73.5 and 52.7%, respectively, in MCF-7, and by 84.5 and 62.6% in T-47D cells. At high concentrations: 5x10(-6) and 5x10(-5) mol/l, medrogestone has no effect on MCF-7 cells, but inhibits the sulfotransferase activity in T-47D cells by -31.4% at 5x10(-5) mol/l. In conclusion, the inhibitory effect provoked by medrogestone on the enzyme involved in the biosynthesis of E2 (sulfatase pathway) in estrogen-dependent breast cancer, as well as the stimulatory effect on the formation of the inactive ES, support a probable anti-proliferative effect of this progestin in breast tissue. Clinical applications of these findings can open new therapeutic possibilities for this disease.
Chetrite
G S
GS
Hormones and Cancer Research Unit, Paris, France.
Ebert
C
C
Wright
F
F
Philippe
A C
AC
Pasqualini
J R
JR
D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism; D004970:Estrone / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D008524:Medrogestone / Q000008:administration & dosage / Q000494:pharmacology*; D045167:Progesterone Congeners / Q000008:administration & dosage / Q000494:pharmacology*; D013429:Sulfatases / Q000378:metabolism*; D015238:Sulfotransferases / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D018931:Antineoplastic Agents, Hormonal; D045167:Progesterone Congeners; D008524:Medrogestone; D004970:Estrone; D004958:Estradiol; D015238:Sulfotransferases; D013429:Sulfatases; C017296:estrone sulfate