Induction of neutrophilic differentiation of human promyelocytic leukemic cells by branched-chain carboxylic acid anticonvulsant drugs.
The anticonvulsant drug 1-methyl-1-cyclohexanecarboxylic acid ( MCCA ) has been shown to cause maturation of murine neuroblastoma cells in vitro at concentrations that are pharmacologically achievable. HL-60 human promyelocytic leukemia cells cultured with this drug underwent a dose-dependent decrease in growth. Similarly, neutrophilic differentiation, based on morphologic criteria and the acquisition of the ability to reduce nitroblue tetrazolium and phagocytose yeast, was observed. Valproic acid, a clinically available anticonvulsant that is chemically related to MCCA , likewise inhibited growth and promoted maturation of HL-60 cells, although only at concentrations above the recommended therapeutic blood levels. MCCA was additive in its ability to induce differentiation of HL-60 with retinoic acid, another compound that induces differentiation at pharmacologic concentrations. MCCA , or similar branched-chain fatty acids, may be useful in the treatment of human leukemia, particularly in combination with other differentiation-inducing drugs.
D000927:Anticonvulsants / Q000627:therapeutic use; D000970:Antineoplastic Agents; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003509:Cyclohexanecarboxylic Acids / Q000494:pharmacology*; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D009504:Neutrophils / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology; D014635:Valproic Acid / Q000494:pharmacology
D000927:Anticonvulsants; D000970:Antineoplastic Agents; D003509:Cyclohexanecarboxylic Acids; C027655:1-methylcyclohexanecarboxylic acid; D014212:Tretinoin; D014635:Valproic Acid