Attenuation of photodynamically induced apoptosis by an RGD containing peptide.
Research efforts have focused on the improvement of already established photodynamic therapy (PDT) protocols. The use of adjunct therapies is one such route. The integrin class of receptors mediates extracellular matrix signals through a complex maze of intertwining cellular pathways. The Arg-Gly-Asp (RGD) motif is known to bind to several of the 25 known integrin receptor types. Soluble RGD peptides under most circumstances induce apoptosis in a number of cell lines In this study, the effect of an RGD-containing peptide on the photodynamic action of aluminium disulfophthalocyanine (A1PcS(2adj)) was investigated. Adenocarcinoma lung cancer cells (A549) and murine mammary cancer cells (EMT-6) were treated with A1PcS(2adj) in the presence of soluble RGD. At elevated RGD concentrations (10 mM) apoptosis was induced by the peptide alone. It was shown that at lower concentrations, RGD abrogated the apoptotic effect of PDT in both cell lines, as assessed by an MTT cytotoxicity assay, nucleosomal DNA laddering and the formation of apoptotic bodies. RGD protection against apoptosis was more pronounced in the A549 receptor positive cell line which exhibits over 70% cell survival when using 100 microM RGD peptide under LD90 conditions. Different parameters were investigated to clearly establish that the attenuation of cell killing was not solely due to quenching of the excited species by the peptide. Indeed, the phenomenon is not photophysical but biological.
Allen
Cynthia M
CM
Department of Nuclear Medicine and Radiobiology, Université de Sherbrooke, Sherbrooke, Québec, Canada J1H 5N4.
Sharman
Wesley M
WM
La Madeleine
Carole
C
van Lier
Johan E
JE
Weber
Joseph M
JM
D006801:Humans; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000737:chemistry*; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D026082:Singlet Oxygen; D014407:Tumor Cells, Cultured
D009842:Oligopeptides; D010455:Peptides; D026082:Singlet Oxygen; C047981:arginyl-glycyl-aspartic acid