Modulation of redox signal transduction pathways in the treatment of cancer.
Reactive oxygen species (ROS)-mediated damage to DNA is associated with induction of stress-activated protein kinases leading to secondary and tertiary effects on the nuclear matrix, cytoplasmic transport mechanisms, and altered mitochondrial and cell membranes. The cellular defenses against ROS damage are associated with up-regulation of gene products that can significantly alter cell biology, including antiapoptotic Bax family proteins and inflammatory proteins. Altered cell integrity can occur either directly or by indirect paracrine and juxtacrine interactions within tissues. Previous approaches toward therapeutic intervention against ROS damage have included administration of radical scavenger compounds, use of novel drugs that increase cellular production of constitutive antioxidants, or pharmacologic agents that modify the intracellular transport of antioxidants. Strategies to modify the cellular effects of ROS in hyperbaric oxygen injury to the lung, reperfusion injury to transplanted organs, and cancer have led to novel approaches of gene therapy in which the transgenes for antioxidant proteins can be expressed in specific tissues. Reducing tissue-damaging effects of ROS may have relevance to cancer patients by ameliorating normal tissue damage from ionizing irradiation therapy, photodynamic therapy, and cancer chemotherapy.
Greenberger
J S
JS
Department of Radiation Oncology, University of Pittsburgh Cancer Institute, University of Pittsburgh Medical Center, PA 15213, USA. greenbergerjs@msx.upmc.edu
Kagan
V E
VE
Pearce
L
L
Boriseniao
G
G
Tyurina
Y
Y
Epperly
M W
MW
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy; D002460:Cell Line; D016207:Cytokines / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004579:Electron Transport / Q000528:radiation effects; D016166:Free Radical Scavengers / Q000627:therapeutic use; D015316:Genetic Therapy / Q000379:methods; D005978:Glutathione / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009369:Neoplasms / Q000378:metabolism / Q000517:prevention & control / Q000628:therapy*; D010084:Oxidation-Reduction; D011837:Radiation-Protective Agents / Q000627:therapeutic use; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000235:genetics* / Q000502:physiology / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D000975:Antioxidants; D016207:Cytokines; D016166:Free Radical Scavengers; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; D005978:Glutathione