Distinct transduction mechanisms of cyclooxygenase 2 gene activation in tumour cells after photodynamic therapy

Volanti, Cédric; Hendrickx, Nico; Lint, Johan Van; Matroule, Jean-Yves; Agostinis, Patrizia; Piette, Jacques

doi:10.1038/sj.onc.1208481

Cited by 35 publications

(28 citation statements)

References 42 publications

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“…Given the important role of the p38 MAPK pathway in hypericin-PDT in T24 cells [5,6] we found it imperative to add evidence confirming HO-1 as a potential p38 MAPK downstream target in our paradigm. To this end we silenced the expression of p38 MAPK in T24 cells, subjected them to the photodynamic treatment and monitored the expression of HO-1 as a function of time.…”

Section: Hypericin-pdt Induces Ho-1 At the Mrna And Protein Levels Inmentioning

confidence: 99%

“…cDNA were prepared in a 20 µl final volume with 1 µg RNA as described in [6]. 2 µl cDNA were mixed with 10 µl SYBR Green Mix (Applied Biosystems, Warrington, UK) and with 270 nM forward (5 CTGAGTTCATGAGGAACTTTCA-GAAG 3 ) and 270 nM reverse (5 TGGTACAGGGAGGC-CATCAC 3 ) HO-1 primers or with 300 nM forward (5 GAGTATGCCTGCCGTGTG 3 ) and 300 nM reverse (5 AATCCAAATGCGGCATCT 3 ) β2-microglobulin (B2M) primers in a 20 µl final volume.…”

Section: Quantitative Rt-pcrmentioning

confidence: 99%

“…We have recently reported that following exposure of tumor cells to PDT different signal transduction pathways are engaged leading to the expression of the inducible cyclooxygenase-2 (COX-2) [5,6], a master enzyme involved in the conversion of arachidonic acid to PGE 2 , with a documented tumor promoting role [7]. In particular, up-regulation of the COX-2 protein levels by hypericin-PDT is mediated by the stabilization of the COX-2 transcript through the specific activation of the p38 MAPK signaling pathway [5].…”

Section: Introductionmentioning

confidence: 99%

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Induction of heme-oxygenase 1 requires the p38MAPK and PI3K pathways and suppresses apoptotic cell death following hypericin-mediated photodynamic therapy

et al. 2007

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Photodynamic therapy (PDT) is an established anticancer modality utilizing the photogeneration of reactive oxygen species (ROS) to kill the cancer cells and hypericin is a promising photosensitizer for the treatment of bladder tumors. In this paper we characterize the signaling pathways and the mechanisms leading to the up-regulation of the antioxidant enzyme heme oxygenase (HO-1) in PDT treated cancer cells. We show that PDT engages the p38(MAPK) and PI3K signaling cascades for HO-1 induction. p38(MAPK) inhibitors or small interfering RNA (siRNA) for p38(MAPK) suppress HO-1 induction after PDT and complete repression is attained when p38 and PI3K antagonists are combined. Blocking these signaling pathways increases additively the propensity of the cells to undergo PDT-induced apoptosis, mirroring the effect of HO-1 silencing. Conversely, increasing HO-1 protein level by hemin prior to irradiation is cytoprotective. HO-1 stimulation by PDT is dependent on transcription and de novo protein synthesis and it is preceded by the nuclear accumulation of the Nrf2 transcription factor, which is reduced by inhibitors of p38(MAPK) and PI3K. Altogether these results indicate that stimulation of HO-1 expression by hypericin-PDT is a cytoprotective mechanism governed by the p38(MAPK) and PI3K pathways, likely through the control of the nuclear availability of the Nrf2 pool.

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Section: Hypericin-pdt Induces Ho-1 At the Mrna And Protein Levels Inmentioning

confidence: 99%

Section: Quantitative Rt-pcrmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Induction of heme-oxygenase 1 requires the p38MAPK and PI3K pathways and suppresses apoptotic cell death following hypericin-mediated photodynamic therapy

et al. 2007

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“…Another study that focused on the molecular mechanisms regulating COX-2 expression after low-dose PDT in HeLa and T24 cancer cell line reported PDT induced COX-2 expression in these cells. This expression was attributed to nuclear factor kappa B (NFjB)-dependent transcription of COX-2 gene without any post-transcriptional regulation, thereby promoting cancer cell regrowth following PDT [49]. To summarize, recent studies have demonstrated that porphyrin and chlorin-e6 PDT induce the expression of COX-2 and MAPK, and NF-jB pathway activates COX-2 expression in hypericin-mediated PDT.…”

Section: Cyclooxygenase-2mentioning

confidence: 99%

The effect of photodynamic therapy on tumor angiogenesis

Ramaswamy

Gan

Soo

et al. 2009

Cell. Mol. Life Sci.

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Photodynamic therapy (PDT), the activation of a photosensitive drug in tumor tissue with light of specific wavelength, has been used effectively to treat certain solid tumors. Though therapeutic responses are encouraging, PDT-mediated oxidative stress can act as an angiogenic switch that ultimately leads to neovascularization and tumor recurrence. This article explores the effect of PDT on angiogenesis in different tumor models. Overexpression of proangiogenic vascular endothelial growth factor, cyclooxygenase-2 and matrix metalloproteases has often been reported post-illumination. Recent clinical studies have demonstrated that inhibiting angiogenesis after chemotherapy and radiotherapy is an attractive and valuable approach to cancer treatment. In this review, we report the effective therapeutic strategy of combining angiogenesis inhibitors with PDT to control and treat tumors.

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“…It seems that the oxidative stress generated after PDT activates a cascade of proteinkinases including p38, with a role in increasing the expression of COX-2. The molecular mechanisms that modulate the expression of COX-2 in tumor cells involve the NF-kB dependent transcription of the COX-2 gene, without the involvement of other mechanisms of post-transcriptional regulation (Hendrickx et al, 2003;Volanti et al, 2005).…”

Section: Pdt Effect On Cox-2mentioning

confidence: 99%