Use of Oxidizing Dyes in Combination with 2-Cyanocinnamic Acid to Enhance Hyperthermic Cytotoxicity in L929 Cells1

Two widely used oxidizing dyes, 2,3,5-triphenyltetrazoliumchloride and méthylà ̈ne blue, can greatly potentiate hyperthermic cytotoxicity whenadministeredsimultaneouslywith 2-cyanocinnamicacid. The same compoundsare virtually nontoxic to L929 cells if administered alone at 42°Cor in combinationwith 2-cyanocinnamicacid at 37°C. Cytotoxicity was synergisticallyenhanced by the combinedregimensafter 3 h of heat exposure. Quercetin, a bioflavonoid known to enhance hyperthermic cytotoxicity,also acts synergistically when administered in combination with 2-cyanocinnamicacid and this effect is apparent after l h of heat exposure. Since these compoundsdo not greatly interfere with pyruvate metabolism at either normal or heat shock temperatures, a mechanism of action based on depletion of NAl)(P)H is considered.