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Most cancer cells are dependent on glucose uptake to fulfil their energy requirements. 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-deoxy-D-[1-(3)H]-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 microM. 2-Hydroxyestradiol and estrone sulfate had little effect on glucose 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 therefore examined the effect of exposing cells to 2-MeOEMATE or paclitaxel for 24 h on basal or insulin stimulated glucose uptake. Using these conditions, 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 therapeutic potential for the treatment of breast cancer.

Type

Journal article

Journal

Mol Cell Endocrinol

Publication Date

25/02/2000

Volume

160

Pages

61 - 66

Keywords

Antineoplastic Agents, Biological Transport, Active, Breast Neoplasms, Deoxyglucose, Estradiol, Estrone, Female, Humans, Hydroxyestrones, Insulin, Kinetics, Paclitaxel, Tumor Cells, Cultured