Induction of heme-oxygenase 1 requires the p38MAPK and PI3K pathways and suppresses apoptotic cell death following hypericin-mediated photodynamic therapy
| العنوان: | Induction of heme-oxygenase 1 requires the p38MAPK and PI3K pathways and suppresses apoptotic cell death following hypericin-mediated photodynamic therapy |
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| المؤلفون: | Esther Buytaert, Jean-Yves Matroule, Peter de Witte, Jacques Piette, Patrizia Agostinis, Silvia Kocanova, Jakub Golab |
| المساهمون: | Laboratoire de biologie moléculaire eucaryote (LBME), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre de Biologie Intégrative (CBI), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS) |
| المصدر: | Apoptosis Apoptosis, Springer Verlag, 2007, 12 (4), pp.731-41 |
| بيانات النشر: | Springer Science and Business Media LLC, 2007. |
| سنة النشر: | 2007 |
| مصطلحات موضوعية: | MAPK/ERK pathway, Radiation-Sensitizing Agents, Cancer Research, Small interfering RNA, MAP Kinase Signaling System, NF-E2-Related Factor 2, medicine.medical_treatment, Clinical Biochemistry, Pharmaceutical Science, Apoptosis, Photodynamic therapy, Biology, p38 Mitogen-Activated Protein Kinases, Phosphatidylinositol 3-Kinases, 03 medical and health sciences, 0302 clinical medicine, Cell Line, Tumor, Neoplasms, medicine, Humans, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, Enzyme Inhibitors, RNA, Small Interfering, Perylene, Transcription factor, PI3K/AKT/mTOR pathway, Phosphoinositide-3 Kinase Inhibitors, 030304 developmental biology, Anthracenes, Pharmacology, 0303 health sciences, Biochemistry (medical), Cell Biology, 3. Good health, Cell biology, Heme oxygenase, Photochemotherapy, Enzyme Induction, 030220 oncology & carcinogenesis, Cancer cell, Signal transduction, Heme Oxygenase-1 |
| الوصف: | 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. |
| تدمد: | 1573-675X 1360-8185 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ab84692c6b757d974a4d063f6390cf7cTest https://doi.org/10.1007/s10495-006-0016-xTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....ab84692c6b757d974a4d063f6390cf7c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 1573675X 13608185 |
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