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Reactions of Bis(thiosemicarbazonato) Copper(II) complexes with tumor cells and mitochondria

✍ Scribed by Christine H. Chan-Stier; Daniel Minkel; David H. Petering

Publisher
Elsevier Science
Year
1976
Weight
811 KB
Volume
6
Category
Article
ISSN
0006-3061

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✦ Synopsis

The respiration of Ehrlich ascites tumor cells is inhibited by 3-ethoxy-2-oxobutyraldehyde bis (thiosemicarbazanato) copper (II). State 3 oxidative phosphorylation in mitochondria from tumor cells is also inhibited, with the effect more pronounced using glutamate or pyruvate-malate as substrates than with succinate. The disruption of oxidative phosphorylation in bovine heart mitochondria is qualitatively similar. The principal site of inhibition is in coupling site one, energetically between the electron transport site chain and the locus of uncoupling by 2,4-dinitrophenol. This appears to contain thiol groups which are oxidized by the complex. For a series of bis (thiosemicarbazonato) copper complexes, the extent of inhibition of heart mitochondrial oxidative phosphorylation is correlated with the reduction potentials of the complexes and with their in vitro cytotoxic effects against Walker 256 carcinoma tumor cells.

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