Effect of 5-aminolevulinic acid-mediated photodynamic therapy on MCF-7 and MCF-7/ADR cells

Background and Objectives: Photodynamic therapy (PDT) has been proposed as an alternative approach in overcoming multidrug resistance (MDR) phenotype. To verify whether 5-aminolevulinic acid (A-LA)-mediated PDT is effective in MDR cells, we studied the protoporphyrin IX (PpIX) content, intracellular localization, and phototoxicity in human breast cancer cells MCF-7 and derived MDR subline, MCF-7/ADR. Study Design/Materials and Methods: The fluorescence kinetics of ALA-induced PpIX was evaluated by spectrofluorometer. The phototoxicity of MCF-7 and MCF7/ADR cells was determined by tetrazolium (MTT) assays and clonogenic assay. Furthermore, Annexin V and propidium iodide (PI) binding assays were performed to analyze the characteristics of cell death after ALA-PDT. Results: MCF-7/ADR accumulated a lower level of PpIX as compared to parental MCF-7 cells. Significant phototoxicity was observed in MCF-7 and increased in a fluence-dependent manner with LD50 around 8 J/cm(2). Compared to its parental counterpart, MCF-7/ADR cells were less sensitive to ALA photodynamic treatment and PDT-induced cytotoxicity did not increase in a dose responsive manner as the concentration of ALA increased or the fluence of light increased. ALA-PDT was less effective for MCF-7/ADR cells than MCF-7 cells even under the condition when these two cell lines contained the similar amounts of PpIX. Conclusions: These results indicate that, except for the MDR related characteristics, MCF-7/ADR cells might possess intrinsic mechanisms that render them less sensitive to AIA-PDT induced phototoxicity. (C) 2004 Wiley-Liss, Inc.