Selective enhancement of cellular oxidative stress by chloroquine: implications for the treatment of glioblastoma multiforme.
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.
Toler
Steven M
SM
Department of Clinical Pharmacology, Pfizer, Incorporated, 50 Pequot Avenue, New London, Connecticut 06320, USA. steven.m.toler@pfizer.com
Noe
Dennis
D
Sharma
Amarnath
A
D000818:Animals; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000378:metabolism / Q000532:radiotherapy* / Q000601:surgery; D002738:Chloroquine / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D003497:Cyclic N-Oxides / Q000494:pharmacology / Q000627:therapeutic use; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D006427:Hemin / Q000378:metabolism; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects; D007501:Iron / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008247:Lysosomes / Q000187:drug effects; D008563:Membrane Lipids / Q000737:chemistry; D016877:Oxidants / Q000494:pharmacology* / Q000627:therapeutic use; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010961:Plasmodium / Q000187:drug effects; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology* / Q000627:therapeutic use; D012717:Sesquiterpenes / Q000494:pharmacology / Q000627:therapeutic use; D013113:Spin Labels
D037621:Artemisinins; D003497:Cyclic N-Oxides; D008563:Membrane Lipids; D016877:Oxidants; D011838:Radiation-Sensitizing Agents; D012717:Sesquiterpenes; D013113:Spin Labels; C069269:ferriprotoporphyrin IX-chloroquine complex; D006427:Hemin; D002738:Chloroquine; C031327:artemisinin; D007501:Iron; C001803:tempol