Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on 17β-estradiol-induced glucose metabolism in MCF-7 human breast cancer cells: 13C nuclear magnetic resonance spectroscopy studies

T. R. Narasimhan, S. Safe, H. J. Williams, A. I. Scott

Research output: Contribution to journalArticle

20 Scopus citations


The effects of 17β-estradiol, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and their combination on the metabolism of [1-13C] glucose were determined in cell suspensions of wild-type MCF-7 human breast cancer cells, by 13C NMR spectroscopy. Preliminary studies showed that, during the 7-hr duration of the NMR experiment, the cells maintained their viability and their aryl hydrocarbon responsiveness. Lactate was the major glucose metabolite detected in these studies, and the rate of lactate formation in the untreated (control) and 17β-estradiol (10-9 M)-treated cells was 60 and 86 fmol/cell/hr, respectively; this represented a 40% increase in lactate formation in the cells treated with 17β-estradiol; comparable results were observed for the percentage of glucose converted into lactate. In contrast, TCDD (10-9 M) did not significantly alter the rate of glucose metabolism or lactate formation. Co-treatment of the cells with 17β-estradiol (10-9 M) plus TCDD (10-8 to 10-10 M) showed that TCDD completely inhibited the 17β-estradiol-induced metabolism of [13C] glucose to lactate in MCF-7 cells. In contrast, 2,8-dichlorodibenzo-p-dioxin (10-8 M), a weak aryl hydrocarbon receptor agonist, did not inhibit estrogen-induced glucose-to-lactate metabolism in MCF-7 cells. In addition, it was shown that TCDD caused a significant decrease in 17β-estradiol-induced lactate formation within 1 hr after treatment, whereas the induction of monooxygenase activity was not observed until 3 hr after exposure of the cells to TCDD. These data indicate that TCDD-induced 17β-estradiol metabolism is not related to the decrease in the rate of conversion of glucose to lactate. These results further define the antiestrogenic responses elicited by TCDD and show that 13C NMR spectroscopy provides a unique method for measuring, in real time, the effects of TCDD on specific metabolic pathways.

Original languageEnglish (US)
Pages (from-to)1029-1035
Number of pages7
JournalMolecular Pharmacology
Issue number6
StatePublished - 1991

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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