Subcellular localization of merocyanine 540 (MC540) and induction of apoptosis in murine myeloid leukemia cells

Subcellular localization of photosensitizers is thought to play a critical role in determining the mode of cell death after photodynamic treatment (PD T) of leukemia cells. Using confocal laser scanning microscopy and fluoresc ent organelle probes, we examined the subcellular localization of merocyani ne 540 (MC540) in the murine myeloid leukemia M1 and WEHI 3B (JCS) cells. T wo patterns of localization were observed: in JCS cells, MC540 was found to localize on the plasma membrane and mitochondria; and in M1 leukemia cells , MC540 was found to localize on lysosomes. The relationship between subcel lular localization of MC540 and PDT-induced apoptosis was investigated. Apo ptotic cell death. as judged by the formation of apoptotic nuclei, was obse rved 4 h after irradiation in both leukemia cell lines. Typical ladders of apoptotic DNA fragments were also detected by DNA gel electrophoresis in PD T-treated JCS and M1 cells. At the irradiation dose of 46 kJ/m(2) (LD90 for JCS and LD86 for M1 cells), the percentage of apoptotic JCS and M1 cells w as 78 and 38%, respectively. This study provided substantial evidence that MC540 localized differentially in the mitochondria. and the subsequent phot odamage of the organelle played an important role in PDT-mediated apoptosis in myeloid leukemia cells.