Quenching of tyrosine radicals of M2 subunit from ribonucleotide reductase in tumor cells by different antitumor agents: an EPR study.
The inhibition of ribonucleotide reductase (RR) of intact Ehrlich ascites tumor cells by different antitumor agents was compared using EPR spectroscopy. The inactivation of M2 subunit was measured via quenching of the functionally essential tyrosine radical. Inhibitors of different classes, for example, hydroxyurea, pyrogallol, and thiosemicarbazones, differ in their efficiency by three orders of magnitude. Most effective inhibition was found for isoquinoline-1-aldehyde-thiosemicarbazone (IQ-1) with an IC50 value of 0.18 microM. Inhibition of RR inside tumor cells is comparable with that reported for isolated enzymes.
Liermann
B
B
Central Institute of Molecular Biology, Academy of Sciences of GDR, Berlin-Buch.
Lassmann
G
G
Langen
P
P
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy / Q000201:enzymology; D004578:Electron Spin Resonance Spectroscopy; D004789:Enzyme Activation; D005609:Free Radicals; D006918:Hydroxyurea / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology*; D051379:Mice; D011748:Pyrogallol / Q000494:pharmacology; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors*; D013882:Thiosemicarbazones / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000378:metabolism*
D000970:Antineoplastic Agents; D005609:Free Radicals; D013882:Thiosemicarbazones; D011748:Pyrogallol; D014443:Tyrosine; D012264:Ribonucleotide Reductases; D006918:Hydroxyurea