Inhibition of deoxyglucose uptake in MCF-7 breast cancer cells by 2-methoxyestrone and 2-methoxyestrone-3-O-sulfamate

Most cancer cells are dependent on glucose uptake to fulfil their energy re quirements. In the present investigation we have examined the ability of 2- methoxyestrone (2-MeOE1), 2-methoxyestradiol (2-MeOE2), 2-methoxyestrone-3- O-sulfamate (2-MeOEMATE), and a number of related compounds, to inhibit 2-d eoxy-D-[l-H-3]-glucose uptake in MCF-7 breast cancer cells. Glucose uptake was shown to be linear with respect to cell number and time over a 5-35min period. 2-MeOE2, 2-MeOE1 and 2-MeOEMATE inhibited glucose uptake by 25-49% at 10 mu M. 2-Hydroxyestradiol and estrone sulfate had little effect on glu cose uptake, whereas estrone glucuronide inhibited uptake by 29%. There is evidence that 2-methoxyestrogens may exert an anti-mitotic effect on cells by stabilizing microtubules in a similar manner to that of paclitaxel. We t herefore examined the effect of exposing cells to 2-MeOEMATE or paclitaxel for 24 h on basal or insulin stimulated glucose uptake. Using these conditi ons, 2-MeOEMATE and paclitaxel inhibited basal glucose uptake by 50 and 22% , respectively, and insulin stimulated uptake by 36 and 51%, respectively. The development of drugs that can inhibit glucose uptake could have therape utic potential for the treatment of breast cancer. (C) 2000 Elsevier Scienc e Ireland Ltd. All rights reserved.