How does doxorubicin interfere with actin polymerization?
It is well known that doxorubicin (adriamycin), an antibiotic with an antitumoral action, has some undesirable side effects. Among these, the most serious is, undoubtedly, damage to myocardial tissue (progressive cardiomyopathy). We have for some time focused our attention on the effect of this drug on cellular contractile systems and, more specifically, on the process of actin polymerization, which we consider to be an extremely delicate key point for the economy of most cellular motor manifestations. In the present study, using capillary viscometry, spectrofluorometry and electron microscopy, we have shown a negative action of doxorubicin on various important chemical events which contribute to the transformation of G-actin into F-actin. Specifically, we found that the drug mainly acts by reducing the polymer size. A possible action mechanism of the antibiotic is proposed and a plausible correlation among the events described in vitro and those observed in vivo is advanced.
Colombo
R
R
Department of Biology, University of Milan, Italy.
Milzani
A
A
D000199:Actins / Q000378:metabolism*; D000818:Animals; D004317:Doxorubicin / Q000494:pharmacology*; D007700:Kinetics; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D009132:Muscles / Q000378:metabolism; D011817:Rabbits; D013050:Spectrometry, Fluorescence
D000199:Actins; D046911:Macromolecular Substances; D004317:Doxorubicin