NDLI: Photodynamic targeting of EGFR does not predict the treatment outcome in combination with the EGFR tyrosine kinase inhibitor Tyrphostin AG1478

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Photochemical & Photobiological Sciences Vol - 7 Issue - 8

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Photodynamic targeting of EGFR does not predict the treatment outcome in combination with the EGFR tyrosine kinase inhibitor Tyrphostin AG1478

Content Provider	Royal Society of Chemistry (RSC)
Author	Kaalhus, Olav Berg, Kristian Weyergang, Anette
Copyright Year	2008
Abstract	Photodynamic therapy (PDT) is a selective treatment modality against cancer. PDT is based on the preferential retention of photosensitizers (PSs), in the tumour and subsequent light exposure which activates the PS and generates reactive oxygen species. Multimodality therapy is increasingly relevant in cancer treatment and PDT has been shown as an effective adjuvant to other anti-cancer modalities. The present study reports on the combination of PDT and an epidermal growth factor receptor (EGFR) specific tyrosine kinase inhibitor (TKI), Tyrphostin AG1478. The combination was studied in two cell lines; A-431 and NuTu-19, expressing EGFR and sensitive to Tyrphostin treatment, but with different sensitivity towards photochemical EGFR damage. A-431 cells were treated with the PSmeso-tetraphenylporphine with 2 sulfonate groups on adjacent phenyl rings (TPPS2a) in order to target mainly the endo/lysosomal compartments (18 h incubation followed by a 4 h chase in drug-free medium) or the plasma membrane (30 min incubation) upon light exposure. The EGFR was inhibited after PDT in A-431 cells only when TPPS2a was located on the plasma membrane, but both treatment regimes resulted in synergistic inhibition of cell growth when combined with Tyrphostin. TPPS2a treatment of NuTu-19 cells, designed for endo/lysosomal localization, followed by light attenuated EGFR phosphorylation but resulted in additive or antagonistic effects on cell growth when Tyrphostin was administered prior to or after PDT respectively. It was therefore concluded that photochemical damage of EGFR does not predict the treatment outcome when PDT is combined with Tyrphostin.
Starting Page	1032
Ending Page	1040
Page Count	9
File Format	HTM / HTML PDF
ISSN	1474905X
Volume Number	7
Issue Number	9
Journal	Photochemical & Photobiological Sciences
DOI	10.1039/b806209a
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Estrogen receptor Reactive oxygen species Phosphorylation Photodynamic therapy Cell membrane Tyrphostin Phenyl group EGFR Epidermal growth factor receptor Tyrosine-kinase inhibitor Adjuvant Cancer Growth factor Photochemistry
Content Type	Text
Resource Type	Article
Subject	Physical and Theoretical Chemistry

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