Alendronate, raloxifene and tibolone inhibit the proliferation-stimulating activity of 17(beta)-estradiol in MCF-7 cells

Abstract

Estrogen replacement therapy has been considered for many decades as the gold standard in the management of osteoporosis, but the risk of developing breast cancer outweighs its benefits. It is not known whether addition of another antiresorptive agent to estrogen replacement therapy will provide any beneficial effects against such risk. This in vitro study aimed to investigate the inhibitory effects of alendronate, raloxifene and tibolone on the proliferation-stimulating activity of 17ƒÒ-estradiol in MCF-7 cells. The effects of individual drugs, alendronate, raloxifene and tibolone, alone at concentrations of 10-10-10-4 M and their combinations with 10-8 M 17ƒÒ-estradiol on MCF-7 cell proliferation were determined on day 2 and day 6 of incubation using the standard tetrazolium MTT (cell viability) method. The cytotoxic effect of the drugs either alone or in combination with 17ƒÒ-estradiol was determined by visualizing morphological features of the MCF-7 cells and measuring the release of lactate dehydrogenase (LDH) from the cells. The results indicated that the three drugs inhibited the proliferation of MCF-7 cells in a concentration-related manner on both days of investigation. At all indicated concentrations, they could significantly inhibit (p ƒ¬ 0.001) the proliferation-stimulating activity of 10-8 M 17ƒÒ-estradiol. Among the three drugs, tibolone exhibited the most potent inhibitory effect. Morphological detection and LDH determination revealed a strong cytotoxic activity of these three drugs. Extrapolations from these in vitro data suggest that the three drugs, alendronate, raloxifene and tibolone, do not increase the risk of cancer mediated via estrogen receptors and probably reduce the risk of developing breast cancer in estrogen users.