Journal article
Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy
Redox biology, Vol.10(C), pp.274-284
12/01/2016
DOI: 10.1016/j.redox.2016.10.010
PMCID: PMC5106370
PMID: 27833040
Abstract
Ascorbate (AscH
−
) functions as a versatile reducing agent. At pharmacological doses (P-AscH
−
; [plasma AscH
−
] ≥≈20 mM), achievable through intravenous delivery, oxidation of P-AscH
−
can produce a high flux of H
2
O
2
in tumors. Catalase is the major enzyme for detoxifying high concentrations of H
2
O
2
. We hypothesize that sensitivity of tumor cells to P-AscH
−
compared to normal cells is due to their lower capacity to metabolize H
2
O
2
. Rate constants for removal of H
2
O
2
(
k
cell
) 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 H
2
O
2
was revealed, with the average
k
cell
for normal cells being twice that of tumor cells. The ED
50
(50% clonogenic survival) of P-AscH
−
correlated directly with
k
cell
and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH
−
.
•
Ascorbate oxidizes in cell culture medium to generate a flux of H
2
O
2
.
•
The rate constants for removal of extracellular H
2
O
2
are on average 2-fold higher in normal cells than in cancer cells.
•
The ED
50
of high-dose ascorbate correlated with the ability of tumor cells to remove extracellular H
2
O
2
.
•
The response to pharmacological ascorbate in murine-models of pancreatic cancer paralleled the
in vitro
results.
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Details
- Title: Subtitle
- Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy
- Creators
- Claire M Doskey - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USAVisarut Buranasudja - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USABrett A Wagner - Free Radical & Radiation Biology Program in the Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USAJustin G Wilkes - Department of Surgery, The University of Iowa, Iowa City, IA 52242, USAJuan Du - Department of Surgery, The University of Iowa, Iowa City, IA 52242, USAJoseph J Cullen - Free Radical & Radiation Biology Program in the Department of Radiation Oncology, The University of Iowa, Iowa City, IA 52242, USAGarry R Buettner - Interdisciplinary Graduate Program in Human Toxicology, The University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Redox biology, Vol.10(C), pp.274-284
- DOI
- 10.1016/j.redox.2016.10.010
- PMID
- 27833040
- PMCID
- PMC5106370
- NLM abbreviation
- Redox Biol
- ISSN
- 2213-2317
- eISSN
- 2213-2317
- Publisher
- Elsevier
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 CA169046, R01 GM073929, T32 CA148062, P42 ES013661, P30 ES005605, R01 CA184051; name: The Gateway for Cancer Research; DOI: 10.13039/100011343, name: Holden Comprehensive Cancer Center, award: P30 CA086862
- Language
- English
- Date published
- 12/01/2016
- Academic Unit
- Surgery; Radiation Oncology; Iowa Superfund Research Program
- Record Identifier
- 9984046917502771
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