Preferential binding of cisplatin to mitochondrial DNA and suppression of ATP generation in human malignant melanoma cells.
Effects of cisplatin on mitochondria in human malignant melanoma from gingiva were investigated. Cisplatin bound about 50 times more to mitochondrial DNA than to chromosomal DNA. NADH-ubiquinone reductase was decreased 48 h after the administration to about 40% of the initial level, and cellular ATP level was also depressed at that time. A good correlation was observed between the energy status and NADH-ubiquinone reductase activity. These results suggest that the preferential binding of cisplatin to mitochondrial DNA results in the inhibition of NADH-ubiquinone reductase and consequently in the disturbance of ATP generation.
Murata
T
T
Department of Biochemistry, Mie University School of Medicine, Japan.
Hibasami
H
H
Maekawa
S
S
Tagawa
T
T
Nakashima
K
K
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D002945:Cisplatin / Q000378:metabolism* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D005260:Female; D006801:Humans; D007700:Kinetics; D008545:Melanoma / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004272:DNA, Mitochondrial; D000255:Adenosine Triphosphate; D004247:DNA; D016660:NAD(P)H Dehydrogenase (Quinone); D011808:Quinone Reductases; D004259:DNA-Directed DNA Polymerase; D002945:Cisplatin