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Modulating ALA-PDT efficacy of mutlidrug resistant MCF-7 breast cancer cells using ALA prodrug.
MedLine Citation:
PMID:  22020364     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Multi-drug resistance of breast cancer is a major obstacle in chemotherapy of cancer treatments. Recently it was suggested that photodynamic therapy (PDT) can overcome drug resistance of tumors. ALA-PDT is based on the administration of 5-aminolevulinic acid (ALA), the natural precursor for the PpIX biosynthesis, which is a potent natural photosensitizer. In the present study we used the AlaAcBu, a multifunctional ALA-prodrug for photodynamic inactivation of drug resistant MCF-7/DOX breast cancer cells. Supplementation of low doses (0.2mM) of AlaAcBu to the cells significantly increased accumulation of PpIX in both MCF-7/WT and MCF-7/DOX cells in comparison to ALA, or ALA + butyric acid (BA). In addition, our results show that MCF-7/DOX cells are capable of producing higher levels of porphyrins than MCF-7/WT cells due to low expression of the enzyme ferrochelatase, which inserts iron into the tetra-pyrrol ring to form the end product heme. Light irradiation of the AlaAcBu treated cells activated efficient photodynamic killing of MCF-7/DOX cells similar to the parent MCF-7/WT cells, depicted by low mitochondrial enzymatic activity, LDH leakage and decreased cell survival following PDT. These results indicate that the pro-drug AlaAcBu is an effective ALA derivative for PDT treatments of multidrug resistant tumors.
Authors:
Tamar Feuerstein; Gili Berkovitch-Luria; Abraham Nudelman; Ada Rephaeli; Zvi Malik
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-24
Journal Detail:
Title:  Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology     Volume:  -     ISSN:  1474-9092     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101124451     Medline TA:  Photochem Photobiol Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Microscopy Unit, Ramat-Gan, 52900, Israel.
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