caa a22 4500 606236961 CHVBK 20210128101250.0 cr unu---uuuuu 210128e20150301xx s 000 0 eng 10.1007/s11010-014-2291-0 doi (NATIONALLICENCE)springer-10.1007/s11010-014-2291-0 Bryostatin-1 causes radiosensitization of BMG-1 malignant glioma cells through differential activation of protein kinase-Cδ not evident in the non-malignant AA8 fibroblasts [Elektronische Daten] [Raghubendra Dagur, Shashank Hambarde, Sudhir Chandna] Bryostatin-1 (bryo-1), a non-phorbol ester, is known to sensitize mammalian cells against certain chemotherapeutic drugs. We assessed its ability to modify radiation response of mammalian cells using Chinese hamster fibroblasts AA8 cells and human malignant glioma BMG-1 cells. In the malignant glioma BMG-1 cell line, bryo-1 pre-treatment significantly enhanced radiation-induced growth inhibition and cytogenetic damage, and further reduced the clonogenic cell survival as compared to cells irradiated at the clinically relevant dose of 2Gy. PKCδ expression increased significantly when bryo-1 pre-treated BMG-1 glioma cells were irradiated at 2Gy and induced prolonged ERK-1/2 activation associated with p21 overexpression. Silencing PKCδ resulted in inhibition of bryo-1-induced radiosensitization. In contrast, bryo-1 failed to alter radiosensitivity (cell survival; growth inhibition; cytogenetic damage) or activate ERK1/2 pathway in the AA8 fibroblasts despite PKCδ phosphorylation at its regulatory (Y155) domain, indicating alternate mechanisms in these non-malignant cells as compared to the glioma cells. This study suggests that bryo-1 may effectively enhance the radiosensitivity of malignant cells and warrants further in-depth investigations to evaluate its radiosensitizing potential in various cell types. Springer Science+Business Media New York, 2014 Bryostatin-1 nationallicence PKCδ nationallicence Radiosensitivity nationallicence Ionizing radiation nationallicence Dagur Raghubendra Natural Radiation Response Mechanisms Group, Division of Radiation Biosciences, Institute of Nuclear Medicine & Allied Sciences, Brig. S K Mazumdar Road, Timarpur, 110054, Delhi, India aut Hambarde Shashank Natural Radiation Response Mechanisms Group, Division of Radiation Biosciences, Institute of Nuclear Medicine & Allied Sciences, Brig. S K Mazumdar Road, Timarpur, 110054, Delhi, India aut Chandna Sudhir Natural Radiation Response Mechanisms Group, Division of Radiation Biosciences, Institute of Nuclear Medicine & Allied Sciences, Brig. S K Mazumdar Road, Timarpur, 110054, Delhi, India aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 49-59 0300-8177 401:1-2<49 2015 401 11010 https://doi.org/10.1007/s11010-014-2291-0 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2291-0 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dagur Raghubendra Natural Radiation Response Mechanisms Group, Division of Radiation Biosciences, Institute of Nuclear Medicine & Allied Sciences, Brig. S K Mazumdar Road, Timarpur, 110054, Delhi, India aut NATIONALLICENCE 700 1- Hambarde Shashank Natural Radiation Response Mechanisms Group, Division of Radiation Biosciences, Institute of Nuclear Medicine & Allied Sciences, Brig. S K Mazumdar Road, Timarpur, 110054, Delhi, India aut NATIONALLICENCE 700 1- Chandna Sudhir Natural Radiation Response Mechanisms Group, Division of Radiation Biosciences, Institute of Nuclear Medicine & Allied Sciences, Brig. S K Mazumdar Road, Timarpur, 110054, Delhi, India aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 401/1-2(2015-03-01), 49-59 0300-8177 401:1-2<49 2015 401 11010