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Effect of 5‐aminolevulinic acid‐mediated photodynamic therapy on MCF‐7 and MCF‐7/ADR cells
Author(s) -
Tsai Tsuimin,
Hong RueyLong,
Tsai JuiChang,
Lou PeiJen,
Ling IFang,
Chen ChinTin
Publication year - 2004
Publication title -
lasers in surgery and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.888
H-Index - 112
eISSN - 1096-9101
pISSN - 0196-8092
DOI - 10.1002/lsm.10246
Subject(s) - phototoxicity , photodynamic therapy , protoporphyrin ix , mcf 7 , clonogenic assay , chemistry , propidium iodide , cytotoxicity , mtt assay , erythropoietic protoporphyria , cancer research , cancer cell , cell culture , pharmacology , pheophorbide a , microbiology and biotechnology , apoptosis , in vitro , protoporphyrin , biochemistry , cancer , programmed cell death , medicine , biology , porphyrin , human breast , organic chemistry , genetics
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 (ALA)‐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 MCF‐7/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 LD 50 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 ALA–PDT induced phototoxicity. Lasers Surg. Med. 34:62–72, 2004. © 2004 Wiley‐Liss, Inc.