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: Kiyoko Miyagi, Reynée W Sampson, Maya Sieber-Blum, Fritz Sieber
• Journal: Journal of photochemistry and photobiology. B, Biology (J Photochem Photobiol B) Vol. 70 Issue 3 Pg. 133-44 (Jul 2003) ISSN: 1011-1344 [Print] Switzerland
• PMID: 12962637 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Photosensitizing Agents
• Pyrimidinones
• Receptors, Peptide
• annexin V receptor
• merocyanine dye
• Caspases
• Gentian Violet

Topics

• Animals
• Bone Marrow Purging (methods)
• Caspases (metabolism)
• Cell Line, Tumor
• Cell Survival (radiation effects)
• Drug Resistance, Neoplasm
• Gentian Violet (pharmacology)
• Hematopoietic Stem Cell Transplantation (methods)
• Hematopoietic Stem Cells (pathology)
• Humans
• Mice
• Molecular Structure
• Necrosis
• Neoplasms (pathology)
• Photochemotherapy (methods)
• Photosensitizing Agents (pharmacology)
• Pyrimidinones (pharmacology)
• Receptors, Peptide (metabolism)