title: Lack of inhibition of placental estrone sulfatase and aromatase enzymes by vitamin D3 and its analogs.
abstract: The aromatase and estrone sulfatase enzymes are important sources of biologically active estrogens in postmenopausal women with breast cancer. Promising initial results in the treatment of endocrine-responsive breast cancer have been exhibited by 1 alpha 25-dihydroxyvitamin D3 and the synthetic vitamin D analogues MC903 and EB1089. However, these compounds together with vitamin D3 and vitamin D3 sulfate did not inhibit the human placental aromatase enzyme when assayed up to 20 microns. Only vitamin D3 sulfate and 1 alpha 25-dihydroxyvitamin D inhibited the estrone sulfatase activity in human placental microsomes, albeit at high concentration (32 and 37% inhibition, respectively with 50 microns each inhibitor). It is unlikely that inhibition of aromatase or estrone sulfatase enzymes contribute to the inhibitory effect of this group of compounds on breast cancer cells in vivo.
authors.affiliation: Department of Medical Oncology, St George's Hospital Medical School, London, England.
authors.forename: T R
authors.initials: TR
authors.lastname: Evans
authors.forename: M G
authors.initials: MG
authors.lastname: Rowlands
authors.forename: S S
authors.initials: SS
authors.lastname: Sahota
authors.forename: R C
authors.initials: RC
authors.lastname: Coombes
mesh_terms: D047072:Aromatase Inhibitors; D001943:Breast Neoplasms / Q000188:drug therapy; D002762:Cholecalciferol / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D013429:Sulfatases / Q000037:antagonists & inhibitors*
chemical_list: D047072:Aromatase Inhibitors; D002762:Cholecalciferol; D013429:Sulfatases; C020121:estrone sulfatase