The decrease of mitochondrial NADH dehydrogenase and drug induced apoptosis in doxorubicin resistant A431 cells

Doxorubicin (DOX) resistant A10A cells derived from human squamous carcinom a A431 cells were found to exhibit a smaller degree of apoptosis after DOX treatment as compared to their parent cells. Induction of reactive oxygen s pecies (ROS) formation and mitochondrial depolarization by DOX were more pr onounced in the parent cells than in the A10A cells. The fact that catalase suppressed the DOX effect on ROS induction, mitochondrial depolarization a nd apoptosis in both cell lines suggests an involvement of ROS in the DOX-i nduced apoptosis. To investigate the underlying mechanisms for DOX resistan ce in A10A cells, RT-PCR based differential display was used. One of the cl ones, which was down-regulated in the A10A cells, had sequence homology wit h part of the mitochondrial NADH dehydrogenase III (ND3) gene. NADH dehydro genase plays an important role in generating ROS during DOX treatment. The results indicate that down-regulation of ND3 may at least in part contribut e to the mechanism for A10A cells resistant to DOX-induced apoptosis. (C) 2 000 Elsevier Science Inc. All rights reserved.