Role of the Glutathione Redox Cycle in Acquired and de Novo Multidrug Resistance

• DOI: 10.1126/science.3399900
• Publication Date: 2006-10-05T21:21:15Z
• Authors: Robert A. Kramer; Jehane Zakher; George Kim
• Keywords: Glutathione Peroxidase; Leukemia P388; Rectal Neoplasms; Drug Resistance; Carmustine; Glutathione; 3. Good health; Mice; 03 medical and health sciences; Phenotype; 0302 clinical medicine; Verapamil; Doxorubicin; Colonic Neoplasms; Tumor Cells, Cultured; Animals; Humans; Oxidation-Reduction; NADP; Glutathione Transferase

Drug resistance represents a major obstacle to successful cancer chemotherapy. However, the specific biochemical mechanisms responsible for clinical drug are unknown. In these studies antitumor agent adriamycin was found involve two mechanisms, one that decreased accumulation by P170 mechanism and another altered glutathione redox cycle, an important pathway in detoxification of reactive oxygen. This dual demonstrated cell lines had acquired multidrug-resistant phenotype human colorectal cells with de novo resistance. These support model multidrug includes alterations both cycle.