Effect of the aromatase inhibitor, MEN 11066, on growth of two different MCF-7 sublines

The racemate compound MEN 11066 (1-[(benzofuran-2-yl)(4'-cyanophenyl)methyl ]-1H-1,2,4-triazole) and its enantiomers, (+)-MEN 11623 and (-)-MEN 11622, showed potent and selective aromatase activity on human placental microsome s. In addition, to better evaluate their potency as anticancer drugs, the c ompounds were assayed on testosterone-induced cell proliferation to measure their ability in inhibiting oestrogen-dependent tumour growth. Two differe nt sublines originated from the human breast carcinoma MCF-7 were used. One , named MCF-7(tumour aromatase) (TA), that had maintained its intrinsic aro matase activity, was more sensitive to estradiol or testosterone-induced gr owth than the second subline named MCF-7(human placental aromatase) (hPA). The latter had been transfected with the human placental aromatase cDNA, af ter recognizing that the parental cells had aromatase activity reduced to u ndetectable levels. The MEN compounds completely reverted the testosterone- induced proliferation in both MCF-7(TA) and MCF-7(hPA) cells, while they di d not affect the estradiol-triggered proliferation as a proof of their spec ificity for aromatase enzyme. Interestingly, MCF-7(TA) cells were more susc eptible to the effects of aromatase inhibitors than the MCF-7(hPA) cell. Th ese data suggest the efficacy of aromatase inhibitors in breast cancer when the growth dependency from oestrogen is high and a relatively low aromatas e activity may be extremely important for tumour development. (C) 2000 Else vier Science B.V. All rights reserved.