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

Attila Bebes, Tünde Nagy, Z. Bata-Csörgő, L. Kemény, A. Dobozy, M. Széll

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19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)162-166
Number of pages5
JournalJournal of Photochemistry and Photobiology, B: Biology
Volume105
Issue number2
DOIs
Publication statusPublished - Nov 3 2011

Fingerprint

transporter
Photochemotherapy
therapy
Porphyrins
Keratinocytes
porphyrins
Photosensitizing Agents
light sources
cells
Light
Aminolevulinic Acid
pretreatment
lesions
destruction
tumors
ATP Binding Cassette Transporter, Sub-Family G, Member 2
analogs
proteins
bandwidth
Skin

Keywords

  • ABCG2
  • Keratinocyte
  • Photodynamic therapy
  • Porphyrin
  • Transporter inhibitor

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Biophysics

Cite this

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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.",
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AU - Nagy, Tünde

AU - Bata-Csörgő, Z.

AU - Kemény, L.

AU - Dobozy, A.

AU - Széll, M.

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