Potentiation of the antitumor effect of Merocyanine 540-mediated photodynamic therapy by amifostine and amphotericin B.
Leukemia and lymphoma cells are much more sensitive to Merocyanine 540 (MC540)-mediated photodynamic therapy (PDT) than normal pluripotent hematopoietic stem cells and normal colony forming unit-granulocyte/macrophage progenitors (CFU-GM). By contrast, most solid tumor cells are only moderately sensitive to MC540-PDT. The limited activity against solid tumor cells has detracted from MC540's appeal as a broad-spectrum purging agent. We report here that noncytotoxic concentrations of amifostine (Ethyol, Ethiofos, WR-2721) and amphotericin B used either alone or in combination potentiate the MC540-sensitized photoinactivation of leukemia cells, wild-type small cell lung cancer cells and cisplatin-resistant small cell lung cancer cells. Amphotericin B also enhances the MC540-sensitized photoinactivation of normal CFU-GM, whereas amifostine protects CFU-GM against the cytotoxic action of MC540-PDT. The yield of CD34-positive normal hematopoietic stem and progenitor cells is only minimally diminished by pretreatment with amifostine, amphotericin B or combinations of amifostine plus amphotericin B. Purging protocols that combine MC540-PDT with amifostine or with amifostine plus amphotericin B could offer a simple and effective approach to the purging of autologous stem cell grafts that are contaminated with solid tumor cells or the purging of stem cell grafts from heavily pretreated leukemia patients that contain reduced numbers of normal stem and progenitor cells and, therefore, can ill afford additional losses caused by purging.
Tsujino
Ichiro
I
Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI, USA.
Miyagi
Kiyoko
K
Sampson
Reynée W
RW
Sieber
Fritz
F
D004999:Amifostine / Q000494:pharmacology*; D000666:Amphotericin B / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006412:Hematopoietic Stem Cells / Q000187:drug effects* / Q000473:pathology; D006801:Humans; D007938:Leukemia / Q000473:pathology; D008175:Lung Neoplasms / Q000473:pathology; D008223:Lymphoma / Q000473:pathology; D010778:Photochemotherapy / Q000379:methods; D011744:Pyrimidinones / Q000494:pharmacology*; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology; D014407:Tumor Cells, Cultured
D011744:Pyrimidinones; C003954:merocyanine dye; D000666:Amphotericin B; D004999:Amifostine