title: Inhibition of deoxyglucose uptake in MCF-7 breast cancer cells by 2-methoxyestrone and 2-methoxyestrone-3-O-sulfamate.
abstract: 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.
authors.affiliation: Endocrinology and Metabolic Medicine, Imperial College School of Medicine, St. Mary's Hospital, London, UK.
authors.forename: A
authors.initials: A
authors.lastname: Singh
authors.forename: A
authors.initials: A
authors.lastname: Purohit
authors.forename: H A
authors.initials: HA
authors.lastname: Hejaz
authors.forename: B V
authors.initials: BV
authors.lastname: Potter
authors.forename: M J
authors.initials: MJ
authors.lastname: Reed
mesh_terms: D000077584:2-Methoxyestradiol; D000970:Antineoplastic Agents / Q000494:pharmacology; D001693:Biological Transport, Active / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D004970:Estrone / Q000031:analogs & derivatives* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006894:Hydroxyestrones / Q000494:pharmacology*; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D017239:Paclitaxel / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: C405442:2-methoxyoestrone-3-O-sulphamate; D000970:Antineoplastic Agents; D006894:Hydroxyestrones; D007328:Insulin; D004970:Estrone; D004958:Estradiol; D000077584:2-Methoxyestradiol; D003847:Deoxyglucose; D017239:Paclitaxel; C003655:2-methoxyestrone