Tumor cells have decreased ability to metabolize H2O2: Implications for pharmacological ascorbate in cancer therapy

被引：227

作者：

Doskey, Claire M. ^{[1
]}

Buranasudja, Visarut ^{[1
]}

Wagner, Brett A. ^{[2
]}

Wilkes, Justin G. ^{[3
]}

Du, Juan ^{[3
]}

Cullen, Joseph J. ^{[2
,3
,4
]}

Buettner, Garry R. ^{[1
,2
]}

机构：

[1] Univ Iowa, Interdisciplinary Grad Program Human Toxicol, Iowa City, IA 52242 USA

[2] Univ Iowa, Free Rad & Radiat Biol Program, Dept Radiat Oncol, Iowa City, IA 52242 USA

[3] Univ Iowa, Dept Surg, Iowa City, IA 52242 USA

[4] Vet Affairs Med Ctr, Iowa City, IA 52246 USA

来源：

REDOX BIOLOGY | 2016年 / 10卷

基金：

美国国家卫生研究院;

关键词：

MITOCHONDRIAL-DNA DAMAGE; EXTRACELLULAR HYDROGEN-PEROXIDE; GLUTATHIONE-PEROXIDASE; SUPEROXIDE-DISMUTASE; VITAMIN-C; INDUCED CYTOTOXICITY; ATP DEPLETION; RAT-LIVER; CATALASE; ACID;

D O I：

10.1016/j.redox.2016.10.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Ascorbate (AscH-) functions as a versatile reducing agent. At pharmacological doses (P-AscH(-); [plasma AscH(-)] >=approximate to 20 mM), achievable through intravenous delivery, oxidation of P-AscH-can produce a high flux of H2O2 in 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 H2O2 was revealed, with the average kcell for normal cells being twice that of tumor cells. The ED50 (50% clonogenic survival) of P-AscH(-) correlated directly with kcell and catalase activity. Catalase activity could present a promising indicator of which tumors may respond to P-AscH-.

引用

页码：274 / 284

页数：11

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