Cancer cell selectivity of 5-iodo-6-aminobenzopyrone (INH2BP) and methyl-3,5-diiodo-4(4'-methoxyphenoxy) benzoate (DIME).
The cellular pharmacologic actions, as measured by cell killing, of INH2BP, DIME and INO2BA (+ BSO) were determined in three types of cancer cells and compared to their action on quiescent confluent human foreskin fibroblast (HSF) and pre-confluent growing fibroblasts. The confluent HSF cells were completely refractory to the action of INH2BP and DIME, but were killed by INO2BA (+ BSO). Proliferating HSF and all three tumor cell types were killed by all three drugs. The apparent in vivo tumor specificity of INH2BP and DIME is explained by preferential cell cycle dependent selective drug uptake into tumor cells and by drug metabolism that reverses drug action in less vigorously cycling normal cells. The covalent binding of iodonitrosobenzamide (formed from INO2BA) and its toxicity are regulated by the concentration of GSH, and exhibit no cell cycle selectivity.
Kirsten
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Octamer, Inc. and Octamer Research Foundation, San Leandro, CA 94577, USA.
Kun
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D000970:Antineoplastic Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003374:Coumarins / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007463:Iodobenzoates / Q000494:pharmacology*; D010647:Phenyl Ethers / Q000494:pharmacology*; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D001549:Benzamides; D003374:Coumarins; D004791:Enzyme Inhibitors; D007463:Iodobenzoates; D010647:Phenyl Ethers; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C436733:methyl 3,5-diiodo-4-(4'-methoxyphenoxy)benzoate; C071383:5-iodo-6-amino-1,2-benzopyrone; C090712:iniparib