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Title: Targeted inhibition of p38alpha MAPK suppresses tumor-associated endothelial cell migration in response to hypericin-based photodynamic therapy
Authors: Hendrickx, Nico
Dewaele, Michael
Buytaert, Esther
Marsboom, Glenn
Janssens, Stefan
Van Boven, M
Vandenheede, Jackie
de Witte, Peter
Agostinis, Patrizia #
Issue Date: Nov-2005
Publisher: Academic Press
Series Title: Biochemical and Biophysical Research Communications vol:337 issue:3 pages:928-35
Abstract: Photodynamic therapy (PDT) is an established anticancer modality and hypericin is a promising photosensitizer for the treatment of bladder tumors. We show that exposure of bladder cancer cells to hypericin PDT leads to a rapid rise in the cytosolic calcium concentration which is followed by the generation of arachidonic acid by phospholipase A2 (PLA2). PLA2 inhibition significantly protects cells from the PDT-induced intrinsic apoptosis and attenuates the activation of p38 MAPK, a survival signal mediating the up-regulation of cyclooxygenase-2 that converts arachidonic acid into prostanoids. Importantly, inhibition of p38alpha MAPK blocks the release of vascular endothelial growth factor and suppresses tumor-promoted endothelial cell migration, a key step in angiogenesis. Hence, targeted inhibition of p38alpha MAPK could be therapeutically beneficial to PDT, since it would prevent COX-2 expression, the inducible release of growth and angiogenic factors by the cancer cells, and cause an increase in the levels of free arachidonic acid, which promotes apoptosis.
ISSN: 0006-291X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Biochemistry Section (Medicine) (-)
Vesalius Research Centre (-)
Laboratory for Pharmaceutical Biology (-)
Laboratory of Cell Death Research & Therapy
Laboratory for Molecular Cancer Biology
# (joint) last author

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