Salicylate and several structurally analogous compounds enhance
merocyanine 540 (MC540)-photosensitized killing of
leukemia cells (M. A. Anderson, B. Kalyanaraman, and J. B. Feix,
Cancer Res., 53: 806-809, 1993). In this work, we show that
salicylic acid enhances the binding of MC540 prior to illumination, as well as the light-stimulated uptake of MC540 by target L1210 murine and K562 human
leukemia cells.
Acetylsalicylic acid, 2,3- and
2,5-dihydroxybenzoic acids, and
sodium benzoate also enhance MC540 uptake. The irradiation dose responses for loss of cell survival and enhanced MC540 uptake are well correlated, both being shifted to earlier time points in the presence of
salicylate.
Salicylic acid also enhanced photodynamic cell killing of A549 lung
carcinoma and NIH:OVCAR-3 ovarian
carcinoma cells, two cell types which are relatively resistant to MC540-mediated
photosensitization. Cellular uptake of the anionic, potential-sensitive oxonol
dye, bis-(1,3-dibutylbarbituric acid)-trimethine oxonol, is also increased by
salicylate in a dose-dependent fashion. In contrast, cellular uptake of the cationic cyanine
dye,
3,3'-dihexyloxacarbocyanine, is unaffected by
salicylate. These studies suggest that increased uptake of MC540 is the basis of
salicylate enhancement and that changes in plasma membrane potentials may play a mechanistic role in the potentiation of MC540 binding and cell killing.