Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy.
Ascorbate (AscH-) functions as a versatile reducing agent. At pharmacological doses (P-AscH-; [plasma AscH-] ≥≈20mM), achievable through intravenous delivery, oxidation of P-AscH-can produce a high flux of H2O2in tumors. Catalase is the major enzyme for detoxifying high concentrations of H2O2. We hypothesize that sensitivity of tumor cells to P-AscH-compared to normal cells is due to their lower capacity to metabolize H2O2. Rate constants for removal of H2O2(kcell) and catalase activities were determined for 15 tumor and 10 normal cell lines of various tissue types. A differential in the capacity of cells to remove H2O2was revealed, with the average kcellfor normal cells being twice that of tumor cells. The ED50(50% clonogenic survival) of P-AscH-correlated directly with kcelland catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH-.
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USA.
Claire M
CM
Doskey
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USA.
Visarut
V
Buranasudja
Free Radical & Radiation Biology Program in the Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA.
Brett A
BA
Wagner
Department of Surgery, The University of Iowa, Iowa City, IA 52242, USA.
Justin G
JG
Wilkes
Department of Surgery, The University of Iowa, Iowa City, IA 52242, USA.
Juan
J
Du
Free Radical & Radiation Biology Program in the Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA; Department of Surgery, The University of Iowa, Iowa City, IA 52242, USA; Veterans Affairs Medical Center, Veterans Affairs Medical Center, Iowa City, IA 52246, USA.
Joseph J
JJ
Cullen
Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USA; Free Radical & Radiation Biology Program in the Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USA. Electronic address: garry-buettner@uiowa.edu.
Garry R
GR
Buettner
D000072283:A549 Cells; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000494:pharmacology; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D000975:Antioxidants; D006861:Hydrogen Peroxide; D002374:Catalase; D001205:Ascorbic Acid