Immediate protein targets of photodynamic treatment in carcinoma cells.
Oxidative stress induced in tumor cells undergoing photodynamic treatment (PDT) leads to extensive modification of many proteins in these cells. Protein oxidation mainly gives rise to formation of carbonyls and oxidized thiols. The immediate targets of PDT-induced protein oxidation in A431 tumor cells have been identified using a proteomic approach involving selective biotinylation, affinity purification and mass spectrometric identification of modified proteins. In all, 314 proteins were shown to undergo PDT-mediated oxidative modifications. While abundant structural proteins and chaperones represented a significant fraction of the carbonylated proteins, labeling of proteins containing oxidized thiols allowed identification of many proteins at low abundance and those involved in signaling and redox homeostasis. On the basis of the identification of these proteins, several likely mechanisms of PDT-induced triggering of apoptosis were put forward. This may not only lead to a further understanding of the complex network of cellular responses to oxidative stress, but it may also help in detailed targeting of photodynamic treatment applied to cancer.
Tsaytler
Pavel A
PA
Department of Membrane Enzymology, Bijvoet Center for Biomolecular Research, Utrecht University, Utrecht, The Netherlands.
C O'Flaherty
Martina
M
Sakharov
Dmitri V
DV
Krijgsveld
Jeroen
J
Egmond
Maarten R
MR
D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002846:Chromatography, Affinity; D006801:Humans; D009363:Neoplasm Proteins / Q000187:drug effects*; D018384:Oxidative Stress; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000494:pharmacology; D053719:Tandem Mass Spectrometry
D009363:Neoplasm Proteins; D017319:Photosensitizing Agents