Potentiation of merocyanine 540-mediated photodynamic therapy by salicylate and related drugs. Photochem Photobiol 1995 Oct;62(4):790-9
Date
10/01/1995Pubmed ID
7480156DOI
10.1111/j.1751-1097.1995.tb08731.xScopus ID
2-s2.0-0029379792 (requires institutional sign-in at Scopus site) 7 CitationsAbstract
Simultaneous exposure to merocyanine 540 (MC540) and light of a suitable wavelength kills leukemia, lymphoma and neuroblastoma cells but is relatively well tolerated by normal pluripotent hematopoietic stem cells. This differential phototoxic effect has been exploited in preclinical models and a phase I clinical trial for the extracorporeal purging of autologous bone marrow grafts. Salicylate is known to potentiate the MC540-mediated photokilling of tumor cells. Assuming that salicylate induces a change in the plasma membrane of tumor cells (but not normal hematopoietic stem cells) that enhances the binding of dye molecules it has been suggested that salicylate may provide a simple and effective means of improving the therapeutic index of MC540-mediated photodynamic therapy. We report here on a direct test of this hypothesis in a murine model of bone marrow transplantation as well as in clonal cultures of normal murine hematopoietic progenitor cells. In both systems, salicylate enhanced the MC540-sensitized photoinactivation of leukemia cells and normal bone marrow cells to a similar extent and thus failed to improve the therapeutic index of MC540 significantly. On the basis of a series of dye-binding studies, we offer an alternative explanation for the potentiating effect of salicylate. Rather than invoking a salicylate-induced change in the plasma membrane of tumor cells, we propose that salicylate displaces dye molecules from serum albumin, thereby enhancing the concentration of free (active) dye available for binding to tumor as well as normal hematopoietic stem cells.
Author List
Traul DL, Anderson GS, Bilitz JM, Krieg M, Sieber FAuthor
Fritz Sieber PhD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAnti-Inflammatory Agents, Non-Steroidal
Bone Marrow Transplantation
Drug Synergism
Female
Hematopoietic Stem Cells
Leukemia L1210
Light
Mice
Mice, Inbred C57BL
Mice, Inbred DBA
Oxygen
Photochemotherapy
Photosensitizing Agents
Pyrimidinones
Salicylates
Salicylic Acid
Serum Albumin, Bovine
Singlet Oxygen
Tumor Cells, Cultured
