Overexpression of manganese superoxide dismutase promotes the survival of prostate cancer cells exposed to hyperthermia.
It has been hypothesized that exposure of cells to hyperthermia results in an increased flux of reactive oxygen species (ROS), primarily superoxide anion radicals, and that increasing antioxidant enzyme levels will result in protection of cells from the toxicity of these ROS. In this study, the prostate cancer cell line, PC-3, and its manganese superoxide dismutase (MnSOD)-overexpressing clones were subjected to hyperthermia (43 degrees C, 1 h). Increased expression of MnSOD increased the mitochondrial membrane potential (MMP). Hyperthermic exposure of PC-3 cells resulted in increased ROS production, as determined by aconitase inactivation, lipid peroxidation, and H2O2 formation with a reduction in cell survival. In contrast, PC-3 cells overexpressing MnSOD had less ROS production, less lipid peroxidation, and greater cell survival compared to PC-3 Wt cells. Since MnSOD removes superoxide, these results suggest that superoxide free radical or its reaction products are responsible for part of the cytotoxicity associated with hyperthermia and that MnSOD can reduce cellular injury and thereby enhance heat tolerance.
Venkataraman
Sujatha
S
Department of Radiation Oncology, Free Radical and Radiation Biology Program, EMRB 68, The University of Iowa, Iowa City, IA 52242-1101, USA. Sujatha-venkataraman@uiowa.edu
Wagner
Brett A
BA
Jiang
Xiaohong
X
Wang
Hong P
HP
Schafer
Freya Q
FQ
Ritchie
Justine M
JM
Patrick
Burns C
BC
Oberley
Larry W
LW
Buettner
Garry R
GR
D000154:Aconitate Hydratase / Q000037:antagonists & inhibitors / Q000378:metabolism; D002470:Cell Survival; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005334:Fever; D005609:Free Radicals / Q000378:metabolism; D006358:Hot Temperature; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D008564:Membrane Potentials; D008928:Mitochondria / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism*; D013481:Superoxides / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D013481:Superoxides; D006861:Hydrogen Peroxide; D013482:Superoxide Dismutase; D000154:Aconitate Hydratase