Metal ions modulate the effect of doxorubicin on actin assembly.
Doxorubicin (DXR) exhibits a significant activity in many human malignant neoplasms but, unfortunately, produces many undesirable cellular troubles which mainly lead to a severe dose-dependent cardiomyopathy. Many Authors had suggested that doxorubicin interacts with actin and affects the intracellular ion composition; following this reasoning, we studied the effect of doxorubicin on actin polymerization in vitro induced by different metal ions. In this paper we show that the negative action of doxorubicin on actin polymerization (inhibition of filament growth, reduction of polymer amount and polymer size at steady-state) is strongly ion-dependent. With this finding, we suggest that the direct action of antibiotic on actin assembly, in the presence of the drug-related changes in cytoplasmic electrolyte pattern, could become predominant in vivo.
Colombo
R
R
University of Milan, Dept. of Biology, Italy.
Dalle Donne
I
I
Milzani
A
A
D008841:Actin Cytoskeleton / Q000187:drug effects*; D000199:Actins / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004317:Doxorubicin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D011817:Rabbits
D000199:Actins; D004317:Doxorubicin; D008274:Magnesium; D011188:Potassium; D002118:Calcium