Modification of extracorporeal photopheresis technology with porphyrin precursors. Comparison between 8-methoxypsoralen and hexaminolevulinate in killing human T-cell lymphoma cell lines in vitro

• Published in: Biochimica et biophysica acta Vol. 1840; no. 9; pp. 2702 - 2708
• Main Authors: Čunderlíková, B., Vasovič, V., Randeberg, L.L., Christensen, E., Warloe, T., Nesland, J.M., Peng, Q.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.09.2014
• Subjects: Aminolevulinic Acid - analogs & derivatives; Aminolevulinic Acid - pharmacology; Cell Proliferation - drug effects; Cell Proliferation - radiation effects; Cell Survival - drug effects; Cell Survival - radiation effects; Extracorporeal photopheresis; Hexaminolevulinate; Humans; Jurkat Cells; Lymphoma, T-Cell - drug therapy; Lymphoma, T-Cell - pathology; Methoxsalen - pharmacology; Photodynamic therapy; Photopheresis; Photosensitizing Agents - pharmacology; Protoporphyrin IX; Psoralen; Ultraviolet Rays; Ultraviolet-A light; PDT; UV; Extracorporeal photopheresis; Photodynamic therapy; CTCL; GvHD; PpIX; MTS; MOP; HAL; Psoralen; ECP; PUVA; ALA; FBS; Ultraviolet-A light; PI; Hexaminolevulinate; Protoporphyrin IX
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2014.05.020

Extracorporeal photopheresis that exposes isolated white blood cells to 8-methoxypsoralen (8-MOP) and ultraviolet-A (UV-A) light is used for the management of cutaneous T-cell lymphoma and graft-versus-host disease. 8-MOP binds to DNA of both tumor and normal cells, thus increasing the risk of carcinogenesis of normal cells; and also kills both tumor and normal cells with no selectivity after UV-A irradiation. Hexaminolevulinate (HAL)-induced protoporphyrin-IX is a potent photosensitizer that localizes at membranous structures outside of the nucleus of a cell. HAL-mediated photodynamic therapy selectively destroys activated/transformed lymphocytes and induces systemic anti-tumor immunity. The aim of the present study was to explore the possibility of using HAL instead of 8-MOP to kill cells after UV-A exposure. Human T-cell lymphoma Jurkat and Karpas 299 cell lines were used to evaluate cell photoinactivation after 8-MOP and/or HAL plus UV-A light with cell proliferation and long term survival assays. The mode of cell death was also analyzed by fluorescence microscopy. Cell proliferation was decreased by HAL/UV-A, 8-MOP/UV-A or HAL/8-MOP/UV-A. At sufficient doses, the cells were killed by all the regimens; however, the mode of cell death was dependent on the treatment conditions. 8-MOP/UV-A produced apoptotic death exclusively; whereas both apoptosis and necrosis were induced by HAL/UV-A. 8-MOP can be replaced by HAL to inactivate the Jurkat and Karpas 299 T-cell lymphoma cells after UV-A irradiation via apoptosis and necrosis. This finding may have an impact on improved efficacy of photopheresis. •8-MOP can be replaced by HAL to inactivate human T-cell lymphoma cells after UV-A.•8-MOP/UV-A induces only apoptosis; while HAL/UV-A causes apoptosis and necrosis.•This finding may have an impact on improved efficacy of photopheresis