Distinct transduction mechanisms of cyclooxygenase 2 gene activation in tumour cells after photodynamic therapy.
Photodynamic therapy (PDT) is a minimally invasive treatment for cancer and several noncancerous proliferating cell diseases. PDT relies on the uptake of a photosensitizing compound by the pathologic tissue followed by a selective irradiation with visible light, which leads to oxidative stress-mediated cell death. However, some studies showed that PDT induces the release of proangiogenic factors, such as vascular endothelial growth factor, and/or cyclooxygenase-2 (COX-2), thereby promoting cancer cell regrowth following PDT. In this work, we focused on the molecular mechanisms regulating COX-2 expression after low-dose PDT in two cancer cell lines, namely HeLa and T24. We report that PDT induces COX-2 expression in these cells and this expression is mainly due to nuclear factor kappa B (NF-kappaB)-dependent transcription of cox-2 gene without any post-transcriptional regulation. However, the transduction mechanism leading to NF-kappaB activation and subsequent cox-2 gene transcription differs in both cell types. In T24, NF-kappaB activation occurs through a protein kinase C (PKC)alpha- and phosphoinositide-3-kinase (PI3K)-dependent I kappa B kinase (IKK) complex activation, whereas in HeLa cells, NF-kappaB activation is mediated by PKC- and PI3K-independent IKK complex activation.
Volanti
Cedric
C
Laboratory of Virology and Immunology, Institute of Pathology B23, University of Liège, B-4000 Liège, Belgium.
Hendrickx
Nico
N
Van Lint
Johan
J
Matroule
Jean-Yves
JY
Agostinis
Patrizia
P
Piette
Jacques
J
D051546:Cyclooxygenase 2; D004789:Enzyme Activation / Q000187:drug effects; D051550:I-kappa B Kinase; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009369:Neoplasms / Q000188:drug therapy*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010778:Photochemotherapy; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D014407:Tumor Cells, Cultured
D051546:Cyclooxygenase 2; D051550:I-kappa B Kinase; D007527:Isoenzymes; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D011451:Prostaglandin-Endoperoxide Synthases; D011493:Protein Kinase C; D017346:Protein Serine-Threonine Kinases