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.