Glucose Deprivation-induced Cytotoxicity and Alterations in Mitogen-activated Protein Kinase Activation Are Mediated by Oxidative Stress in Multidrug-resistant Human Breast Carcinoma Cells

In the studies described here, we demonstrate that mitogen-activated protein kinase was activated within 3 min of being in glucose-free medium and remained activated for 3 h

Yong J. Lee; Sandra S. Galoforo; Christine M. Berns; Jenn C. Chen; Bruce H. Davis; Julia E. Sim; Peter M. Corry; Douglas R. Spitz

2002

Scholarcy highlights

  • We have previously observed that glucose deprivation activates mitogen-activated protein kinase1 and induces cell death in multidrug-resistant human breast carcinoma MCF-7/ADR cells
  • In addition the thiol antioxidant, N-acetyl-L-cysteine, rescued cells from glucose deprivation-induced cytotoxicity and suppressed MAPK activation. These results suggest that glucose deprivation-induced cytotoxicity and alterations in MAPK signal transduction are mediated by oxidative stress in MCF-7/ADR
  • We demonstrate that glucose deprivationinduced cell death in MCF-7/ADR is accompanied by activation of the MAPK pathway as well as oxidative stress as evidenced by significant increases in intracellular oxidized glutathione content and pro-oxidant production
  • These results indicate that treatment with a thiol antioxidant was capable of inhibiting both the cytotoxicity and the alterations in MAPK signal transduction induced by glucose deprivation in the MCF-7/ADR cells
  • The major finding of this work is that glucose deprivationinduced oxidative stress appears to account for the cytotoxicity and alterations in MAPK signal transduction which were observed in MCF-7/ADR cells
  • Glucose deprivation-induced oxidative stress clearly involves a disruption in the steady state levels of total and reduced glutathione levels in the MCF-7/ADR cells
  • Our observations suggest that the prolonged activation of mitogen-activated protein kinase caused by metabolic oxidative stress could represent an attempt by the cells to induce protective mechanisms to try and alleviate the cytotoxic effects of glucose deprivation

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