Abstract
Chloroquine is used in the treatment of malaria, a disease caused by infection with the parasite Plasmodium. Although chloroquine appears to possess diverse pharmacological activity, its plasmodicidal activity results from augmentation of parasite oxidative stress. Chloroquine also appears to augment oxidative stress in metabolically active mammalian cells, including human astroglial cells. The authors propose that chloroquine may augment oxidative stress induced by radiotherapy in the treatment of glioblastoma multiforme, enhancing therapeutic efficacy. Such an effect would be consistent with the known pharmacological effects of chloroquine observed in Plasmodium. Other selective redox agents, such as tempol and artemisinin, should be investigated clinically for therapeutic benefit when coadministered with combined radio- and chemotherapy for cancer.
MeSH terms
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Animals
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Artemisinins / pharmacology
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Artemisinins / therapeutic use
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Brain Neoplasms / metabolism
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Brain Neoplasms / radiotherapy*
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Brain Neoplasms / surgery
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Chloroquine / metabolism
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Chloroquine / pharmacology*
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Chloroquine / therapeutic use
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Cyclic N-Oxides / pharmacology
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Cyclic N-Oxides / therapeutic use
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Glioblastoma / drug therapy*
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Glioblastoma / metabolism
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Glioblastoma / radiotherapy
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Glioblastoma / surgery
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Hemin / metabolism
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Humans
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Intracellular Membranes / drug effects
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Iron / metabolism
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Lipid Peroxidation / drug effects
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Lysosomes / drug effects
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Membrane Lipids / chemistry
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Oxidants / pharmacology*
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Oxidants / therapeutic use
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Oxidation-Reduction
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Oxidative Stress / drug effects*
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Plasmodium / drug effects
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Radiation-Sensitizing Agents / pharmacology*
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Radiation-Sensitizing Agents / therapeutic use
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Sesquiterpenes / pharmacology
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Sesquiterpenes / therapeutic use
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Spin Labels
Substances
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Artemisinins
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Cyclic N-Oxides
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Membrane Lipids
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Oxidants
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Radiation-Sensitizing Agents
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Sesquiterpenes
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Spin Labels
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ferriprotoporphyrin IX-chloroquine complex
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Hemin
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Chloroquine
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artemisinin
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Iron
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tempol