Oxidative stress and apoptosis: a new treatment paradigm in cancer.
Redox regulation has been shown to be an important component of malignant cell survival. Tipping the cellular redox balance through pharmacologic regulation in favor of increasing intracellular reactive oxygen species (ROS) and/or depleting protective reducing metabolites (such as glutathione and nicotinamide adenine dinucleotide phosphate) may lead to oxidative stress and resultant induction of apoptosis for the treatment of cancer. We review the biology and importance of ROS with regard to malignant and normal cells. Moreover, we discuss pre-clinical and clinical data regarding novel therapeutic agents that modulate the cellular redox system including buthionine sulfoximine, ascorbic acid, arsenic trioxide, imexon, and motexafin gadolinium as single-agents and in combination. Continued research is needed to better understand the mechanisms and specific apoptotic pathways involved in ROS-induced cell death, as well as, to determine the most rationale and effective combination of redox-active agents.
Engel
Ryan H
RH
Division of Hematology/Oncology, Northwestern University Feinberg School of Medicine, The Robert H. Lurie Comprehensive Cancer Center, Chicago, IL 60611, USA.
Evens
Andrew M
AM
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D017209:Apoptosis; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000008:administration & dosage; D001205:Ascorbic Acid / Q000008:administration & dosage; D019328:Buthionine Sulfoximine / Q000008:administration & dosage; D016923:Cell Death; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000378:metabolism; D006588:Hexanones / Q000008:administration & dosage; D006801:Humans; D008665:Metalloporphyrins / Q000008:administration & dosage; D008954:Models, Biological; D008956:Models, Chemical; D009369:Neoplasms / Q000473:pathology* / Q000628:therapy*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010087:Oxides / Q000008:administration & dosage; D017382:Reactive Oxygen Species
D000964:Antimetabolites, Antineoplastic; D001152:Arsenicals; D006588:Hexanones; D008665:Metalloporphyrins; D010087:Oxides; D017382:Reactive Oxygen Species; D019328:Buthionine Sulfoximine; C014919:4-imino-1,3-diazabicyclo(3.1.0)hexan-2-one; C437683:motexafin gadolinium; D005978:Glutathione; D001205:Ascorbic Acid; D000077237:Arsenic Trioxide