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Specific inhibition of the ABCG2 transporter could improve the efficacy of photodynamic therapy.
MedLine Citation:
PMID:  21911299     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Photodynamic therapy is based on the selective accumulation of a photosensitizer in tumors, followed by destruction of the target tissue by a light source. Protoporphyrin IX, a well-known photosensitizer, was recently reported as an endogenous substrate for the multidrug transporter ABCG2. We investigated the role of ABCG2 protein in the porphyrin extrusion ability of keratinocytes, with regard to the impact of the specific inhibition of ABCG2 by a non-toxic fumitremorgin C analog, Ko-134, on photodynamic therapy efficacy. We studied the level of porphyrin accumulation in response to delta-aminolevulinic acid pretreatment in proliferating and highly differentiated HaCaT keratinocytes. An in vitro model of photodynamic therapy on HaCaT cells was established with a therapeutically approved narrow-bandwidth red-light source. The porphyrin extrusion ability of HaCaT cells proved to correlate with their ABCG2 expression which was higher in proliferating cells than in differentiated cells. Moreover, the specific inhibition of ABCG2 by Ko-134 enhanced the sensitivity of keratinocytes to photodynamic therapy in vitro. These results suggest that ABCG2 may serve as a target molecule via which to improve the photodynamic therapy of skin lesions: its inhibition by the non-toxic Ko-134 is a promising therapeutic modality.
Authors:
Attila Bebes; Tünde Nagy; Zsuzsanna Bata-Csörgő; Lajos Kemény; Attila Dobozy; Márta Széll
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-23
Journal Detail:
Title:  Journal of photochemistry and photobiology. B, Biology     Volume:  -     ISSN:  1873-2682     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-9-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8804966     Medline TA:  J Photochem Photobiol B     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011 Elsevier B.V. All rights reserved.
Affiliation:
Department of Dermatology and Allergology, University of Szeged, Korányi fasor 6, Szeged H-6720, Hungary.
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