LACK OF INHIBITION OF PLACENTAL ESTRONE SULFATASE AND AROMATASE ENZYMES BY VITAMIN-D-3 AND ITS ANALOGS

The aromatase and estrone sulfatase enzymes are important sources of b iologically active estrogens in postmenopausal women with breast cance r. Promising initial results in the treatment of endocrine-responsive breast cancer have been exhibited by 1 alpha 25-dihydroxyvitamin D-3 a nd the synthetic vitamin D analogues MC903 and EB1089. However, these compounds together with vitamin D-3 and vitamin D-3 sulfate did not in hibit the human placental aromatase enzyme when assayed up to 20 pm. O nly vitamin D-3 sulfate and 1 alpha 25-dihydroxyvitamin D inhibited th e estrone sulfatase activity in human placental microsomes, albeit at high concentration (32 and 37% inhibition, respectively with 50 mu m e ach inhibitor). It is unlikely that inhibition of aromatase or estrone sulfatase enzymes contribute to the inhibitory effect of this group o f compounds on breast cancer cells in vivo.