Nd Maria Cornellier was the study dietitian. This study was supported by a grant from the Ronald P. and Joan M. Nordgren Cancer Analysis Fund, NIH grant RO1 CA120381, and Cancer MEK1 Inhibitor supplier Center Support Grant P30 CA046592. The study applied core sources supported by a Clinical Translational Science Award, NIH grant UL1RR024986 (the Michigan Clinical Study Unit), the Michigan Diabetes Study Center NIH grant 5P60 DK020572 (Chemistry Laboratory), plus the Michigan Nutrition and Obesity Investigation Center NIH grant P30 DK089503.Cancer Prev Res (Phila). Author manuscript; offered in PMC 2014 November 01.Porenta et al.PageAbbreviationsFADS1 FADS2 AA EPA DHA MUFA PUFA SFA Fatty Acid Desaturase 1(Delta-5 desaturase) Fatty Acid Desaturase two (Delta-6 desaturase) Arachidonic Acid (20:4, n-6) Eicosapentaenoic Acid (20:5, n-3) SIRT2 Activator supplier Docosahexaenoic Acid Monounsaturated Fatty Acids Polyunsaturated Fatty Acids Saturated Fatty AcidsNIH-PA Author Manuscript NIH-PA Author Manuscript NIH-PA Author Manuscript
INTERNATIONAL JOURNAL OF ONCOLOGY 43: 375-382,Radiation-induced upregulation of telomerase activity escapes PI3-kinase inhibition in two malignant glioma cell linesP. MILLET1,5, C. GRANOTIER1-4, O. ETIENNE1-4 and F.D. BOUSSIN1-CEA, DSV-IRCM-SCSR, Laboratory of Radiopathology, UMR 967, F-92260 Fontenay-aux-Roses; INSERM, UMR 967, F-92260 Fontenay-aux-Roses; 3Univ Paris Diderot, Sorbonne Paris Cit? UMR 967, F-92260 Fontenay-aux-Roses; 4Univ Paris-Sud, UMR 967, F-92260 Fontenay-aux-Roses, France Received March ten, 2013; Accepted April 19, 2013 DOI: ten.3892/ijo.2013.Abstract. Tumor relapse immediately after radiotherapy is often a terrific concern in the therapy of high-grade gliomas. Inhibition on the PI3-kinase/AKT pathway is known to radiosensitize cancer cells and to delay their DNA repair right after irradiation. In this study, we show that the radiosensitization of CB193 and T98G, two high-grade glioma cell lines, by the PI3K inhibitor LY294002, correlates with all the induction of G1 and G2/M arrest, but is inconsistently linked to a delayed DNA doublestrand break (DSBs) repair. The PI3K/AKT pathway has been shown to activate radioprotective components which include telomerase, whose inhibition may well contribute to the radiosensitization of cancer cells. Nonetheless, we show that radiation upregulates telomerase activity in LY-294002-treated glioma cells also as untreated controls, demonstrating a PI3K/AKT-independent pathway of telomerase activation. Our study suggests that radiosensitizing strategies depending on PI3-kinase inhibition in high-grade gliomas can be optimized by additional treatment options targeting either telomerase activity or telomere upkeep. Introduction Glioblastoma multiforme (GBM) is definitely the most typical as well as the most aggressive brain tumor using a median survival of only 15 months (1,2). Regardless of conjugated surgery, radiotherapy and chemotherapy most sufferers die within the initial year of diagnosis (three,4). The molecular mechanisms implicated inside the resistance of glioblastoma to chemotherapies and radiotherapies overlap with those implicated in oncogenesis (five). Among these, the PI3K/AKT pathway which can be implicated inCorrespondence to: Dr Pascal Millet,Aix-Marseille Univ, CNRS, NICN, UMR 7259, North Health-related Faculty, CS 811, 51 Bd Pierre Dramard, 13344 Marseille Cedex 15, France E-mail: [email protected] address:Key words: telomerase, radiation, PI3-kinase, radiosensitization,glioma, glioblastomaregulation of cell proliferation, cell cycle, survival, apoptosis, migration and angioge.