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


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.
Tsai
Tsuimin
T
Graduate Institute of Biomedical Materials, Taipei Medical University, Taipei 110, Taiwan.
Hong
Ruey-Long
RL
Tsai
Jui-Chang
JC
Lou
Pei-Jen
PJ
Ling
I-Fang
IF
Chen
Chin-Tin
CT
D000622:Aminolevulinic Acid / Q000009:adverse effects / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects*; D006801:Humans; D008928:Mitochondria / Q000187:drug effects; D010778:Photochemotherapy / Q000009:adverse effects; D017319:Photosensitizing Agents / Q000009:adverse effects / Q000494:pharmacology*
D017319:Photosensitizing Agents; D000622:Aminolevulinic Acid