Journal article
Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation
The Biochemical journal, Vol.418(1), pp.29-37
02/15/2009
DOI: 10.1042/BJ20081258
PMCID: PMC2678564
PMID: 18937644
Abstract
Cancer cells, relative to normal cells, demonstrate increased sensitivity to glucose-deprivation-induced cytotoxicity. To determine whether oxidative stress meditated by O-2(center dot-) and hydroperoxides contributed to the differential susceptibility of human epithelial cancer cells to glucose deprivation, the oxidation of DHE (dihydroethidine; for O-2(center dot-)) and CDCFH2 [5- (and 6-)carboxy-2',7'-dichlorocliliydrofluorescein diacetate; for hydroperoxides] was measured in human colon and breast cancer cells (H729, HCT116, SW480 and MB231) and compared with that in normal human cells [FHC cells, 33Co cells and HMECs (human mammary epithelial cells)]. Cancer cells showed significant increases in DHE (2-20-fold) and CDCFH2 (1.8-10-fold) oxidation, relative to normal cells, that were more pronounced in the presence of the mitochondrial electron-transport-chain blocker, antimycin A. Furthermore, HCT116 and MB231 cells were more susceptible to glucose-deprivation-induced cytotoxicity and oxidative stress, relative to 33Co cells and HMECs. HT29 cells were also more susceptible to 2DG (2-deoxy-glucose)-induced cytotoxicity, relative to FHC cells. Overexpression of manganese SOD (superoxide dismutase) and mitochondrially targeted catalase significantly protected HCT116 and MB231 cells from glucose-deprivation-induced cytotoxicity and oxidative stress and also protected HT29 cells from 2DG-induced cytotoxicity. These results show that cancer cells (relative to normal cells) demonstrate increased steady-state levels of ROS (reactive oxygen species; i.e. O-2(center dot-) and H2O2) that contribute to differential susceptibility to glucose-deprivation-induced cytotoxicity and oxidative stress. These studies support file hypotheses that cancer cells increase glucose metabolism to compensate for excess metabolic production of ROS and that inhibition of glucose and hydroperoxide metabolism may provide a biochemical target for selectively enhancing cytotoxicity and oxidative stress in human cancer cells.
Details
- Title: Subtitle
- Increased levels of superoxide and H2O2 mediate the differential susceptibility of cancer cells versus normal cells to glucose deprivation
- Creators
- Nukhet Aykin-Burns - University of IowaIman M. Ahmad - Hashemite UniversityYueming Zhu - University of IowaLarry W. Oberley - University of IowaDouglas R. Spitz - Hashemite University
- Resource Type
- Journal article
- Publication Details
- The Biochemical journal, Vol.418(1), pp.29-37
- DOI
- 10.1042/BJ20081258
- PMID
- 18937644
- PMCID
- PMC2678564
- NLM abbreviation
- Biochem J
- ISSN
- 0264-6021
- eISSN
- 1470-8728
- Publisher
- Portland Press Ltd
- Number of pages
- 9
- Grant note
- R01-CA100045; P42-ES013661; R01-CA115438; P30-CA086862; F32-CA110611 / NIH (National Institutes of Health; Bethesda, MD, U.S.A); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P42ES013661 / NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) P30CA086862; F32CA110611; R01CA115438; R01CA100045; P01CA066081 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 02/15/2009
- Academic Unit
- Pathology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984312989502771
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