title: Crystal violet combined with Merocyanine 540 for the ex vivo purging of hematopoietic stem cell grafts.
abstract: The purpose of this study was to determine in a preclinical purging model, how effective crystal violet-mediated photodynamic therapy (CV-PDT) is against solid tumor and drug-resistant mutant tumor cells, and if certain limitations of CV-PDT can be overcome by using crystal violet (CV) in combination with the membrane-active photosensitizer, Merocyanine 540 (MC540). When used under conditions that preserved an adequate fraction of normal human granulocyte/macrophage progenitors (CFU-GM), CV-PDT failed to achieve meaningful reductions of DU145 prostate, H69 small cell lung cancer, and MDA-MB-435S breast cancer cells. Melphalan-resistant L1210/L-PAM1, adriamycin-resistant P388/ADR, and adriamycin-resistant HL-60/ADR leukemia cells were markedly less sensitive to CV-PDT than their wild-type counterparts, whereas cisplatin-resistant H69/CDDP cells were more sensitive than wild-type H69 cells. Sequential exposure to MC540- and CV-PDT under conditions that preserved an adequate fraction (73% and 29%, respectively) of normal CD34-positive hematopoietic stem cells and granulocyte/macrophage progenitors was highly effective against H69 (99.997% reduction) and H69/CDDP (99.999% reduction) cells, but ineffective against HL-60/ADR, MDA-MB-435S, and DU145 cells. CV thus shows only limited promise as a single-modality purging agent. However, in certain situations, clinically meaningful tumor cell depletions can be obtained by using CV in combination with a second photosensitizer such as MC540.
authors.affiliation: Department of Pediatrics, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
authors.forename: Kiyoko
authors.initials: K
authors.lastname: Miyagi
authors.forename: Reynée W
authors.initials: RW
authors.lastname: Sampson
authors.forename: Maya
authors.initials: M
authors.lastname: Sieber-Blum
authors.forename: Fritz
authors.initials: F
authors.lastname: Sieber
mesh_terms: D000818:Animals; D016465:Bone Marrow Purging / Q000379:methods*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000528:radiation effects; D019008:Drug Resistance, Neoplasm; D005840:Gentian Violet / Q000494:pharmacology*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods; D006412:Hematopoietic Stem Cells / Q000473:pathology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009336:Necrosis; D009369:Neoplasms / Q000473:pathology*; D010778:Photochemotherapy / Q000379:methods*; D017319:Photosensitizing Agents / Q000494:pharmacology; D011744:Pyrimidinones / Q000494:pharmacology*; D018000:Receptors, Peptide / Q000378:metabolism
chemical_list: D017319:Photosensitizing Agents; D011744:Pyrimidinones; D018000:Receptors, Peptide; C080707:annexin V receptor; C003954:merocyanine dye; D020169:Caspases; D005840:Gentian Violet