Dose-dependence of doxorubicin effect on actin assembly in vitro.
Doxorubicin (Adriamycin), one of the most potent antibiotics used in tumor chemotherapy, shows many undesirable side effects. We studied the effect of different drug concentrations on the biochemistry of cell motility and, in particular, on potassium-induced actin polymerization. It is well known, in fact, that the actin aggregational status could dramatically influence many cell motility manifestations. Our results clearly show that stoichiometric and substoichiometric amounts of doxorubicin negatively influence actin polymerization by inhibiting both the filament growth and the polymer amount at steady-state; the balance between the two different effects seems to be in relation to the drug concentration. The obtained results could explain some of the doxorubicin effects previously observed in vivo.
Colombo
R
R
University of Milan, Department of Biology, Italy.
Necco
A
A
Vailati
G
G
Milzani
A
A
D000199:Actins / Q000502:physiology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D011108:Polymers; D011485:Protein Binding / Q000187:drug effects
D000199:Actins; D011108:Polymers; D004317:Doxorubicin