Cardiotoxicity and antitumor activity of a copper(II)-doxorubicin chelate.
The cardiotoxic and cytotoxic effects of the Cu(II)-doxorubicin (DXR) complex [Cu(DXR)]n are compared with those of the parent drug. It is shown that 10(-4) M [Cu(DXR)]n has no depressant effects on isolated rat atria, in contrast with an equimolar concentration of the parent drug. No differences were found between the cytotoxic activities of the Cu(II) complex and free DXR on B16 melanoma and HeLa cells. A reduced penetration of the polymeric [Cu(DXR)]n into the myocardial cells as compared with the free drug was invoked to account for the absence of cardiotoxicity of the DXR complex. On the other hand, the observation that copper-complexation does not affect the cytotoxicity of the drug suggests that extracellular as well as intracellular mechanisms may be involved in the development of its antitumor activity.
Monti
E
E
Istituto di Farmacologia, Università di Milano, Italy.
Paracchini
L
L
Piccinini
F
F
Malatesta
V
V
Morazzoni
F
F
Supino
R
R
D000818:Animals; D000970:Antineoplastic Agents; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D004578:Electron Spin Resonance Spectroscopy; D005260:Female; D006367:HeLa Cells; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D066298:In Vitro Techniques; D008546:Melanoma, Experimental / Q000473:pathology; D009200:Myocardial Contraction / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; C053169:doxorubicin-copper(II) complex; D004317:Doxorubicin