Journal of photochemistry and photobiology. B, Biology, 2011-11, Vol.105 (2), p.162-166
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Specific inhibition of the ABCG2 transporter could improve the efficacy of photodynamic therapy
- Ist Teil von
- Journal of photochemistry and photobiology. B, Biology, 2011-11, Vol.105 (2), p.162-166
- Ort / Verlag
- Switzerland: Elsevier B.V
- Erscheinungsjahr
- 2011
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- ► 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. 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1011-1344eISSN: 1873-2682DOI: 10.1016/j.jphotobiol.2011.08.007Titel-ID: cdi_crossref_primary_10_1016_j_jphotobiol_2011_08_007
- Format
- –
- Schlagworte
- ABCG2, ATP Binding Cassette Transporter, Sub-Family G, Member 2, ATP-Binding Cassette Transporters - antagonists & inhibitors, ATP-Binding Cassette Transporters - genetics, ATP-Binding Cassette Transporters - metabolism, Biological Transport - drug effects, Cell Line, extrusion, Gene Expression Regulation - drug effects, Humans, Indoles - chemistry, Indoles - pharmacology, inhibition, Keratinocyte, keratinocytes, Keratinocytes - drug effects, Keratinocytes - metabolism, Keratinocytes - radiation effects, Neoplasm Proteins - antagonists & inhibitors, Neoplasm Proteins - genetics, Neoplasm Proteins - metabolism, neoplasms, photobiology, photochemistry, Photochemotherapy - methods, Photodynamic therapy, Porphyrin, Porphyrins - metabolism, protoporphyrin, red light, skin lesions, therapeutics, therapy, Transporter inhibitor