Inhibition of Anaerobic Glycolysis of Ascites Cancer Cells by Acridine Dyes and Light

Abstract

Low concentrations of certain well-known chemotherapeutic diaminoacridine dyes (acridine orange, acriflavine, and proflavine), but not thiazine dyes (thionine, methylene blue, thionine blue, and new methylene blue), markedly inhibitedanaerobic glycolysis of ascites cancer cells upon illumination with white light. This large, photosensitized inhibition of anaerobic glycolysis appears to be related to the very low oxidation-reduction (O-R) potential (E′₀ in the region of hydrogen overvoltage) of these diaminoacridines, which, upon absorption of the blue-green component of white light, tend to shift the over-all O-R potential of cell systems negatively toward reduction. Imposition of aerobic conditions, which tend to shift the over-all O-R potential of cell systems toward oxidation, reversed the photo-chemically induced inhibition of anaerobic glycolysis. Aerobic glycolysis of ascites cancer cells was stimulated by diaminoacridines in the dark, but light of sufficient intensify could eliminate this stimulation entirely. Anaerobic glycolysis was stimulated in the dark by acriflavine but not by acridine orange or proflavine. In cell-free media, all the diaminoacridines studied catalyzed the quantitative photo-oxidation of reduced diphosphopyridine nucleotide (DPNH₂) by O₂ to form H₂O₂ and thus yielded a new manometric assay for reduced coenzyme.