Use of oxidizing dyes in combination with 2-cyanocinnamic acid to enhance hyperthermic cytotoxicity in L929 cells.
Two widely used oxidizing dyes, 2,3,5-triphenyltetrazolium chloride and methylene blue, can greatly potentiate hyperthermic cytotoxicity when administered simultaneously with 2-cyanocinnamic acid. The same compounds are virtually nontoxic to L929 cells if administered alone at 42 degrees C or in combination with 2-cyanocinnamic acid at 37 degrees C. Cytotoxicity was synergistically enhanced by the combined regimens after 3 h of heat exposure. Quercetin, a bioflavonoid known to enhance hyperthermic cytotoxicity, also acts synergistically when administered in combination with 2-cyanocinnamic acid and this effect is apparent after 1 h of heat exposure. Since these compounds do not greatly interfere with pyruvate metabolism at either normal or heat shock temperatures, a mechanism of action based on depletion of NAD(P)H is considered.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000008:administration & dosage*; D004357:Drug Synergism; D006979:Hyperthermia, Induced; D007942:Leukemia, Experimental / Q000628:therapy*; D008751:Methylene Blue / Q000008:administration & dosage*; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D027501:Monocarboxylic Acid Transporters; D010084:Oxidation-Reduction; D011773:Pyruvates / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000008:administration & dosage*
D002934:Cinnamates; D027501:Monocarboxylic Acid Transporters; D011773:Pyruvates; D013778:Tetrazolium Salts; C018253:alpha-cyanocinnamate; C009591:triphenyltetrazolium; D011794:Quercetin; D008751:Methylene Blue