Role of antioxidant genes for the activity of artesunate against tumor cells.

Research output: Contribution to journalArticle

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Abstract

The antimalaria drug, artesunate (ART), is very cytotoxic in tumor cell lines. The active moiety of ART is an endoperoxide bridge that generates carbon-centered free radicals and oxidative stress upon cleavage. Oxidative stress appears to be necessary for the antimalarial activity of ART. To test whether antioxidant gene expression affects the ART response in tumor cell lines we compared the baseline antioxidant mRNA gene expression in the 55 human tumor cell line panel from the National Cancer Institute Developmental Therapeutics Program to the ART IC50. Thioredoxin reductase expression showed a significant positive correlation to the ART IC50 and catalase expression was inversely correlated with the ART IC50 (p<0.05). WEHI7.2 mouse thymoma cells selected for resistance to hydrogen peroxide or transfected with thioredoxin, manganese superoxide dismutase, catalase or bcl-2 showed resistance to ART compared to the parental cell line. Taken together these data support a role for oxidative stress in the mechanism of ART action in tumor cells and suggest that antioxidant defenses act in combination to affect the cellular response to ART.

Original languageEnglish (US)
Pages (from-to)1231-1235
Number of pages5
JournalInternational Journal of Oncology
Volume23
Issue number4
StatePublished - Oct 2003
Externally publishedYes

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Antioxidants
Genes
Neoplasms
Tumor Cell Line
Inhibitory Concentration 50
Oxidative Stress
Catalase
artesunate
Thioredoxin-Disulfide Reductase
Gene Expression
Thioredoxins
Thymoma
National Cancer Institute (U.S.)
Antimalarials
Hydrogen Peroxide
Superoxide Dismutase
Free Radicals
Carbon
Cell Line
Messenger RNA

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Role of antioxidant genes for the activity of artesunate against tumor cells. / Efferth, Thomas; Briehl, Margaret M; Tome, Margaret E.

In: International Journal of Oncology, Vol. 23, No. 4, 10.2003, p. 1231-1235.

Research output: Contribution to journalArticle

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abstract = "The antimalaria drug, artesunate (ART), is very cytotoxic in tumor cell lines. The active moiety of ART is an endoperoxide bridge that generates carbon-centered free radicals and oxidative stress upon cleavage. Oxidative stress appears to be necessary for the antimalarial activity of ART. To test whether antioxidant gene expression affects the ART response in tumor cell lines we compared the baseline antioxidant mRNA gene expression in the 55 human tumor cell line panel from the National Cancer Institute Developmental Therapeutics Program to the ART IC50. Thioredoxin reductase expression showed a significant positive correlation to the ART IC50 and catalase expression was inversely correlated with the ART IC50 (p<0.05). WEHI7.2 mouse thymoma cells selected for resistance to hydrogen peroxide or transfected with thioredoxin, manganese superoxide dismutase, catalase or bcl-2 showed resistance to ART compared to the parental cell line. Taken together these data support a role for oxidative stress in the mechanism of ART action in tumor cells and suggest that antioxidant defenses act in combination to affect the cellular response to ART.",
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