Nitric oxide reverses drug resistance by inhibiting ATPASE activity of p-glycoprotein in human multi-drug resistant cancer cells

ConclusionsThe reversal of drug resistance is due to inhibition of the ATPase activity by ●NO, resulting in enhancement of the drug accumulation in the MDR cells. Furthermore, DNA damage was not responsible for this reversal of adriamycin resistance. However, formation of adriamycin-dependent toxic free radical species and subsequent cellular damage may be responsible for the increased cytotoxicity of adriamycin by ●NO in NCI/ADR-RES cells.General Significance.Appropriately designed NO donors would be ideal for the treatment of P-gp-overexpressing tumors in the clinic.
Source: Biochimica et Biophysica Acta (BBA) General Subjects - Category: Biochemistry Source Type: research