Mechanism of action of lactoquinomycin A with special reference to the radical formation.
Lactoquinomycin A (LQM-A), an antibiotic containing a quinone moiety in the molecule, inhibited biosyntheses of DNA, RNA and protein to a similar extent in doxorubicin-resistant mouse leukemia L5178Y cells at concentrations higher than 0.08 micrograms/ml. The antibiotic caused cell death in a short period of incubation and the degree of cell death correlated with that of the inhibition of macromolecular syntheses, suggesting that the inhibition of macromolecular syntheses was not a primary effect of LQM-A. LQM-A served as a good electron acceptor, when cytochrome c reductase was used as a quinone reductase. The treatment of the cells with LQM-A significantly reduced cellular NADH and ATP levels. The generation of superoxide radical by LQM-A in cell lysate was observed by reduction of nitro blue tetrazolium, and the production of hydroxyl radical was confirmed by electron spin resonance. The importance of radical formation for the cytotoxicity of LQM-A is discussed.
Nomoto
K
K
Institute of Applied Microbiology, University of Tokyo, Japan.
Okabe
T
T
Suzuki
H
H
Tanaka
N
N
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D007942:Leukemia, Experimental / Q000378:metabolism; D051379:Mice; D009243:NAD / Q000378:metabolism; D009245:NADH Dehydrogenase / Q000378:metabolism; D009285:Naphthoquinones / Q000494:pharmacology; D009696:Nucleic Acids / Q000096:biosynthesis; D014176:Protein Biosynthesis; D013481:Superoxides / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; D009285:Naphthoquinones; D009696:Nucleic Acids; D009243:NAD; C047326:lactoquinomycin A; D013481:Superoxides; D000255:Adenosine Triphosphate; D009245:NADH Dehydrogenase