Pharmacological concentrations of ascorbate radiosensitize glioblastoma multiforme primary cells by increasing oxidative DNA damage and inhibiting G2/M arrest

Free Radical Biology & Medicine
Patries M HerstMelanie J McConnell

Abstract

Glioblastoma multiforme (GBM) has a very poor prognosis because of its chemo- and radiation therapy resistance. Here we investigated the ability of pharmacological concentrations of ascorbate to radiosensitize primary cells isolated from six GBM patients, mouse astrocytoma cells, and mouse astrocytes. We measured cell viability by trypan blue exclusion, generation of double-stranded DNA breaks by H2AX phosphorylation using fluorescently labeled antibodies and FACS analysis, apoptosis by annexin V/propidium iodide staining, inhibition of autophagy by 3-methyladenine, and cell cycle progression by propidium iodide staining of permeabilized cells. We showed that 5 mM ascorbate in combination with 6 Gy radiation killed more GBM primary cells by generating significantly more double-stranded breaks than either treatment alone (p<0.05). Combined treatment affected viability and double-stranded break generation in normal astrocytes to a much smaller extent. Radiation, but not 5 mM ascorbate, caused G2/M arrest in GBM cells and ascorbate prevented radiation-induced G2/M arrest in combined treatment. Cell death in response to 5 mM ascorbate or combination treatment was not mediated by apoptosis or autophagy. In conclusion, pharmacologica...Continue Reading

References

Sep 1, 1978·Proceedings of the National Academy of Sciences of the United States of America·E Cameron, L Pauling
Oct 1, 1976·Proceedings of the National Academy of Sciences of the United States of America·E Cameron, L Pauling
Jan 1, 1988·Annals of the New York Academy of Sciences·C SteinkühlerG Rotilio
Mar 1, 1982·Proceedings of the National Academy of Sciences of the United States of America·P O Seglen, P B Gordon
Mar 18, 2003·Molecular and Cellular Biology·Guozheng GuoJian Jian Li
Apr 8, 2004·Annals of Internal Medicine·Sebastian J PadayattyMark Levine
Jul 6, 2004·International Journal of Radiation Oncology, Biology, Physics·Timothy M Pawlik, Khandan Keyomarsi
Sep 15, 2005·Proceedings of the National Academy of Sciences of the United States of America·Qi ChenMark Levine
Mar 17, 2006·Cancer Research·Sophie Pattingre, Beth Levine
Mar 29, 2006·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·Sebastian J PadayattyMark Levine
Sep 5, 2006·Apoptosis : an International Journal on Programmed Cell Death·Prachee GokhaléMargret C M Vissers
Sep 6, 2006·The Journal of Urology·Wassim KassoufAshish M Kamat
May 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Qi ChenMark Levine
Feb 23, 2008·Free Radical Biology & Medicine·Sarah L CuddihyChristine C Winterbourn
Aug 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Qi ChenMark Levine
Aug 13, 2009·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Amy M McCordPhilip J Tofilon
Jan 14, 2010·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Juan DuJoseph J Cullen
Apr 20, 2010·Autophagy·Joseph J Cullen
Jul 30, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Sabrina FacchinoGilbert Bernier
Mar 16, 2011·Free Radical Biology & Medicine·Michael Graham EspeyQi Chen
Jun 21, 2011·Free Radical Biology & Medicine·Michael GoodmanDean P Jones

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Citations

Apr 30, 2013·Antioxidants & Redox Signaling·Nermi L ParrowMark Levine
Feb 7, 2014·Science Translational Medicine·Melanie J McConnell, Patries M Herst
Aug 6, 2014·Scientific Reports·Marija MojićIvan Spasojević
Mar 18, 2016·Nutrients·Uwe GröberIrenäus A Adamietz
Oct 16, 2015·Canadian Journal of Physiology and Pharmacology·Qi ChenRuochen Dong
Apr 17, 2016·European Journal of Cell Biology·Ana Salomé PiresMaria Filomena Botelho
Mar 31, 2015·BioMed Research International·V NaponelliF Rizzi
Jun 26, 2012·Biochimica Et Biophysica Acta·Juan DuGarry R Buettner
Jan 15, 2015·International Journal of Oncology·Soonduck LeeMyeong-Sok Lee
May 21, 2016·Frontiers in Immunology·Aleli Salazar-RamiroBenjamín Pineda
Jul 25, 2017·Antioxidants·Maria Leticia CastroPatries M Herst
Feb 7, 2018·Dalton Transactions : an International Journal of Inorganic Chemistry·Yingying SunT David Waite
Apr 10, 2019·Journal of Cellular Physiology·Luciano FerradaFrancisco Nualart
Oct 30, 2018·World Journal of Critical Care Medicine·Christoph S Nabzdyk, Edward A Bittner
Jun 11, 2014·Molecular Medicine Reports·Haijin ChenLiping Gao
Sep 8, 2018·Frontiers in Physiology·Anitra C Carr, John Cook
Aug 17, 2017·Nutrition in Clinical Practice : Official Publication of the American Society for Parenteral and Enteral Nutrition·Mary J Marian
Jun 7, 2018·NPJ Precision Oncology·Hongwei LvHongyang Wang
Jun 27, 2020·Frontiers in Oncology·Jianjun ZhouGuodong Wang
Jan 27, 2017·Biomedical Reports·Yoichiro HosokawaEichi Tsuruga
Jul 19, 2018·Frontiers in Physiology·Margreet C M Vissers, Andrew B Das
Sep 20, 2020·Laboratory Investigation; a Journal of Technical Methods and Pathology·Jakub OronowiczStefan Mergler
Jun 18, 2015·Cancer Research·Juan DuJoseph J Cullen
Feb 5, 2021·Antioxidants·Luciano FerradaFrancisco Nualart
Oct 2, 2020·Chemical Research in Toxicology·Anatoly Zhitkovich
Jun 14, 2020·Anti-cancer Agents in Medicinal Chemistry·Dian DayerMajid Kazemi

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