ENHANCEMENT OF MEROCYANINE-540 UPTAKE AND PHOTODYNAMIC CELL-KILLING BY SALICYLATES

Salicylate and several structurally analogous compounds enhance merocy anine 540 (MC540) photosensitized killing of leukemia cells (M. A. And erson, B. Kalyanaraman, and J. B. Feix, Cancer Res., 53: 806-809, 1993 ). In this work, we show that salicylic acid enhances the binding of M C540 prior to illumination, as well as the light-stimulated uptake of MC540 by target L1210 murine and K562 human leukemia cells. Acetylsali cylic acid, 2,3- and 2,5-dihydroxybenzoic acids, and sodium benzoate a lso enhance MC540 uptake. The irradiation dose responses for loss of c ell survival and enhanced MC540 uptake are well correlated, both being shifted to earlier time points in the presence of salicylate. Salicyl ic acid also enhanced photodynamic cell killing of A549 lung carcinoma and NIH:OVCAR-3 ovarian carcinoma cells, two cell types which are rel atively resistant to MC540-mediated photosensitization. Cellular uptak e of the anionic, potential-sensitive oxonol dye, bis-(1,3-dibutylbarb ituric acid)-trimethine oxonol, is also increased by salicylate in a d ose-dependent fashion. In contrast, cellular uptake of the cationic cy anine dye, 3,3'-dihexyloxacarbocyanine, is unaffected by salicylate. T hese studies suggest that increased uptake of MC540 is the basis of sa licylate enhancement and that changes in plasma membrane potentials ma y play a mechanistic role in the potentiation of MC540 binding and cel l killing.