Carboxylic ionophores enhance the cytotoxic potency of ligand- and antibody-delivered ricin A chain.
The highly selective cytotoxicity of site-directed ricin A chain conjugates can be potentiated by membrane-active carboxylic ionophores. The combined use of the two agents results in much faster inactivation of ribosomes and subsequent cell death and lysis. The potency of A chain cytotoxins is correspondingly increased by several orders of magnitude and cells that sparsely express the target antigen or receptor can be killed.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D002460:Cell Line; D003603:Cytotoxins / Q000494:pharmacology*; D004220:Disulfides / Q000494:pharmacology; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology*; D004915:Leukemia, Erythroblastic, Acute / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008985:Monensin / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D011990:Receptors, Transferrin; D012276:Ricin / Q000378:metabolism / Q000494:pharmacology*; D014168:Transferrin / Q000378:metabolism / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D003603:Cytotoxins; D004220:Disulfides; D005663:Furans; D007476:Ionophores; D011956:Receptors, Cell Surface; D011990:Receptors, Transferrin; D014168:Transferrin; D012276:Ricin; D008985:Monensin