TY - JOUR
T1 - Distinct transduction mechanisms of cyclooxygenase 2 gene activation in tumour cells after photodynamic therapy
AU - Volanti, Cedric
AU - Hendrickx, Nico
AU - Van Lint, Johan
AU - Matroule, Jean-Yves
AU - Agostinis, Patrizia
AU - Piette, Jacques
PY - 2005/4/21
Y1 - 2005/4/21
N2 - 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-κB)-dependent transcription of cox-2 gene without any post-transcriptional regulation. However, the transduction mechanism leading to NF-κB activation and subsequent cox-2 gene transcription differs in both cell types. In T24, NF-κB activation occurs through a protein kinase C (PKC)α- and phosphoinositide-3-kinase (PI3K)-dependent I kappa B kinase (IKK) complex activation, whereas in HeLa cells, NF-κB activation is mediated by PKC- and PI3K-independent IKK complex activation.
AB - 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-κB)-dependent transcription of cox-2 gene without any post-transcriptional regulation. However, the transduction mechanism leading to NF-κB activation and subsequent cox-2 gene transcription differs in both cell types. In T24, NF-κB activation occurs through a protein kinase C (PKC)α- and phosphoinositide-3-kinase (PI3K)-dependent I kappa B kinase (IKK) complex activation, whereas in HeLa cells, NF-κB activation is mediated by PKC- and PI3K-independent IKK complex activation.
KW - COX-2
UR - http://www.scopus.com/inward/record.url?scp=18344364385&partnerID=8YFLogxK
U2 - 10.1038/sj.onc.1208481
DO - 10.1038/sj.onc.1208481
M3 - Article
C2 - 15735712
AN - SCOPUS:18344364385
SN - 0950-9232
VL - 24
SP - 2981
EP - 2991
JO - Oncogene
JF - Oncogene
IS - 18
ER -