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Specific inhibition of the ABCG2 transporter could improve the efficacy of photodynamic therapy

Paper ID Volume ID Publish Year Pages File Format Full-Text
30919 44514 2011 5 PDF Available
Title
Specific inhibition of the ABCG2 transporter could improve the efficacy of photodynamic therapy
Abstract

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.

► ABCG2 protein transports the photosensitizer porphyrins out of keratinocytes. ► Proliferation rate of keratinocytes correlates with their porphyrin efflux ability. ► Specific inhibition of ABCG2 by the non toxic Ko-134 improves photodynamic therapy.

Keywords
Keratinocyte; Photodynamic therapy; ABCG2; Porphyrin; Transporter inhibitor
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 105, Issue 2, 3 November 2011, Pages 162–166
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us