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Cyclooxygenase 2-mediated apoptotic and inflammatory responses in photodynamic therapy treated breast adenocarcinoma cells and xenografts

Paper ID Volume ID Publish Year Pages File Format Full-Text
29408 44389 2014 10 PDF Available
Title
Cyclooxygenase 2-mediated apoptotic and inflammatory responses in photodynamic therapy treated breast adenocarcinoma cells and xenografts
Abstract

•COX-2-mediated inflammatory response to PDT is controlled by ROS generation.•The NADPH oxidase participates in regulation of PDT-induced COX-2 expression.•Inhibiting COX-2 decreases in vivo expression of inflammatory and proangiogenic factors.•Inhibition of COX-2 enhances the transcriptional activity of p53 following PDT.•Knockdown of COX-2 increases PDT-induced apoptosis.

Cyclooxygenase 2 (COX-2) is an inducible enzyme that contributes to the generation of chronic inflammation and the development of cancer, and promotes neoplastic transformation, in response to chemical carcinogens and environmental stresses. In this study, we demonstrated that a sublethal dose photodynamic therapy (PDT) led to inflammatory response mediated by the induction of COX-2 and release of Prostaglandin E2 (PGE2). Pretreatment with N-acetylcysteine (NAC) reduced COX-2 expression and PGE2 release induced by PDT. The elevated COX-2 level and PGE2 release following PDT were inhibited by NADPH oxidase inhibitor and NF-κB inhibitor. Inhibition of COX-2 attenuated the levels of PGE2 and vascular endothelial growth factor (VEGF) following PDT in treated tumors, and also decreased the expression of proinflammatory mediators interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, PDT led to an appreciable accumulation of pSer15-p53/COX-2 complexes, and this association of complexes was partially inhibited by SB203580, an inhibitor of p38. Blockage of COX-2 expression by siRNA enhanced the transcriptional activity of p53, and facilitated PDT-induced loss of mitochondrial membrane potential and cleavage of caspase 3, probably due to the elevated Noxa expression disrupting the interaction of Mcl-1/Bax. Together, this study highlights the important roles of COX-2 in PDT-induced apoptosis and inflammation and the specific COX-2-mediated responses to PDT initiated by reactive oxygen species (ROS) involving the regulation of the multiple signaling pathways. These results indicate the inflammatory mediator COX-2 as a potential therapeutic target for improving PDT efficacy.

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Cyclooxygenase 2-mediated apoptotic and inflammatory responses in photodynamic therapy treated breast adenocarcinoma cells and xenografts
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Publisher
Database: Elsevier - ScienceDirect
Journal: Journal of Photochemistry and Photobiology B: Biology - Volume 134, 5 May 2014, Pages 27–36
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us