Anthracycline antitumor drugs weakly inhibit protein kinase C (PKC) activity; this effect is enhanced by coordination with transition metal ions. The present study shows that copper(II) by itself inhibits PKC activity; when Cu(II) is present as the anthracycline-Cu(II) complex [Cu(EpiDXR)2], a significant enhancement is observed as compared to the inhibitory effects of either metal or drug alone. Both regulatory and catalytic sites of PKC are involved in this effect. Electron paramagnetic resonance (EPR) studies indicate an interaction between PKC and Cu(II). It is suggested that Cu(II) is responsible for the inhibitory action of Cu(II)-anthracycline complexes on PKC; anthracycline molecules potentiate this effect, possibly by stabilizing Cu(II) and increasing its availability at enzyme target sites
Monti, E., Monzini, F., Morazzoni, F., Perletti, G., Piccinini, F. (1993). Interaction Of Cu(Ii) And Cu(Ii)-Anthracycline Complexes With Protein-Kinase-C - Spectromagnetic Assessment Of The Inhibitory Effect. INORGANICA CHIMICA ACTA, 205(2), 181-184 [10.1016/S0020-1693(00)85536-X].
Interaction Of Cu(Ii) And Cu(Ii)-Anthracycline Complexes With Protein-Kinase-C - Spectromagnetic Assessment Of The Inhibitory Effect
Morazzoni, F;
1993
Abstract
Anthracycline antitumor drugs weakly inhibit protein kinase C (PKC) activity; this effect is enhanced by coordination with transition metal ions. The present study shows that copper(II) by itself inhibits PKC activity; when Cu(II) is present as the anthracycline-Cu(II) complex [Cu(EpiDXR)2], a significant enhancement is observed as compared to the inhibitory effects of either metal or drug alone. Both regulatory and catalytic sites of PKC are involved in this effect. Electron paramagnetic resonance (EPR) studies indicate an interaction between PKC and Cu(II). It is suggested that Cu(II) is responsible for the inhibitory action of Cu(II)-anthracycline complexes on PKC; anthracycline molecules potentiate this effect, possibly by stabilizing Cu(II) and increasing its availability at enzyme target sitesI documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.