Interactions between bis(guanylhydrazones) and polyamines in isolated mitochondria

The interactions of naturally occurring polyamines: putrescine, spermidine and spermine, with anticancer bis-guanylhydrazones: methylglyoxal-bis(guanylhydrazone) (MGBG) and 4,4'-diacetyldiphenylurea-bis(guanylhydrazone) (DDUG) were investigated at the level of mitochondrial membrane. The effects of bis-guanylhydrazones on intact rat liver mitochondria were readily prevented or reversed by polyamines and these interactions were also affected by the mitochondrial transmembrane potential. Magnesium cations enhanced the protective action of polyamines. The data indicate that competition exists between the essential anticancer bis(guanylhydrazone) and polyamines for low affinity negatively charged binding sites at the outer surface of inner mitochondrial membrane. The study of drug interactions was extended to the level of isolated tumor mitochondria from rat HTC hepatoma and murine L1210 leukemia cells. A complicated pattern of interactions between the anticancer bis-guanylhydrazones and phenethylbiguanide was obtained.