The decrease of mitochondrial NADH dehydrogenease and drug induced apoptosis in doxorubicin resistant A431 cells.
Doxorubicin (DOX) resistant A10A cells derived from human squamous carcinoma A431 cells were found to exhibit a smaller degree of apoptosis after DOX treatment as compared to their parent cells. Induction of reactive oxygen species (ROS) formation and mitochondrial depolarization by DOX were more pronounced in the parent cells than in the A10A cells. The fact that catalase suppressed the DOX effect on ROS induction, mitochondrial depolarization and apoptosis in both cell lines suggests an involvement of ROS in the DOX-induced apoptosis. To investigate the underlying mechanisms for DOX resistance in A10A cells, RT-PCR based differential display was used. One of the clones, which was down-regulated in the A10A cells, had sequence homology with part of the mitochondrial NADH dehydrogenase III (ND3) gene. NADH dehydrogenase plays an important role in generating ROS during DOX treatment. The results indicate that down-regulation of ND3 may at least in part contribute to the mechanism for A10A cells resistant to DOX-induced apoptosis.
Wong
T W
TW
Department of Biochemistry, The Chinese University of Hong Kong, Shatin.
Yu
H Y
HY
Kong
S K
SK
Fung
K P
KP
Kwok
T T
TT
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D002374:Catalase / Q000378:metabolism; D015342:DNA Probes; D018076:DNA, Complementary / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D006801:Humans; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology*; D009245:NADH Dehydrogenase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D015342:DNA Probes; D018076:DNA, Complementary; D007527:Isoenzymes; D017382:Reactive Oxygen Species; D004317:Doxorubicin; D002374:Catalase; D009245:NADH Dehydrogenase