INHIBITION OF ESTROGEN SYNTHESIS IN HUMAN BREAST TUMORS BY TESTOLOLACTONE AND BROMOANDROSTENEDIONE

Article abstract of DOI:10.1016/S0039-128X(80)80007-9

The inhibition of aromatase enzyme in human breast tumors by Δ¹-testololactone, testololactone, 6α-bromoandrostenedione, and 6β-bromoandrostenedione was investigated.Estrone and estradiol synthesis from androstenedione was reduced in 3 tumor incubations by the presence of 0.13 mmol Δ¹-testololactone and testololactone. 6α- and 6β-bromoandrostenedione (2.0 μM) were also shown to block estrogen synthesis in 2 tumors.Furthermore, Lineweaver-Burk plots revealed that all 4 compounds are competitive inhibitors of androstenedione aromatization.An apparent K_m of the aromatase enzyme for androstenedione of 0.08 μM and a V_max of 23 pmol of estrone synthesized/g tumor/hr were determined for one human breast tumor specimen.These results demonstrate that these aromatase inhibitors may be useful for the treatment of breast cancer.