Abstracts from the 2012 BNOS Conference

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ID: 268590
2012
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Abstract
INTRODUCTION: Boswellia derivatives possess pro-apoptotic potential towards glioblastoma in vitro and inhibit cell growth. We investigated whether combining boswellic acid with either clomipramine or temozolomide has synergistic therapeutic potential and whether this would reduce viability of the cancer stem cell (CSC) population. METHOD: Standard and CSC enriched human glioblastoma cell cultures were grown in normoxic and hypoxic conditions. 50 µg/ml of two boswellic acid isomers was administered for 24, 48 and 72 hours before treating with either clomipramine (50 µg/ml for 2 hours) or temozolomide (50 µg/ml for 4 hours). Viability, apoptosis and cell cycle analysis were carried out along with Western blots for cMYC and p21 and ELISAs for Stat3 activation and Bcl-2 levels. RESULTS: In CSC enriched cultures, viability was reduced to around ∼56% after addition of boswellic acid alone and ∼31% in combination with temozolomide but no reduction was observed after treatment with clomipramine and boswellic acid. Cell cycle arrest and apoptosis was induced in up to 95% of glioblastoma cells in vitro while levels of pStat3 were reduced from 83% to 26% in CSC rich cultures. Western blots and ELISAs showed a reduction in cMYC, p21and Bcl-2 levels. CONCLUSION: While addition of clomipramine surprisingly reduced activity of boswellic acid, boswellic acid in combination with temozolomide had an additive effect and reduced cell viability through induction of apoptosis and cell cycle arrest. We reduced viability of CSCs and this may be due to activation of the sustained DNA damage response. These novel findings demonstrate an important therapeutic strategy for exploitation.
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Authors Suzanne Birks,Melis Altinkaya,G. Pilkington,Kathreena M Kurian,Charlene Crosby,Kirsten Hopkins,S. Williams,Laura Donovan,Amy Eason,Viktoria Bosak,Jonathon Holliday,Ivason Corbett,Melanie Keeling,Jacki Bambrough,Jane Simpson,Samantha Higgins,Harjot Dogra,Yuening Zhang,Marcus Bradley,Claudia Schmidberger,Sassan Hafizi,Imran Noorani,S. Price,Aurore Dubocq,Tomasz Jaunky,Clémence Chatelain,Luke Evans,T. Gaissmaier,Qian An,V. Hurwitz,J. Logan,R. Bhangoo,K. Ashkan,A. Gullan,R. Beaney,L. Brazil,S. Kokkinos,R. Blake,A. Singleton,Abigail Shaw,Venkat Iyer,Jennie N Jeyapalan,Isabel Cf Morley,Alfred A Hill,Muhammad A Mumin,Ruth G Tatevossian,Ibrahim Qaddoumi,David W Ellison,Denise Sheer,A. Frary,S. Jefferies,F. Harris,N. Burnet,R. Jena,C. Watts,Brian Haylock,Sophie Leow-Dyke,Nitika Rathi,Helen Wong,Julie Dunn,Atik Baborie,Daniel Crooks,David Husband,Adi Shenoy,Andrew Brodbelt,Carol Walker,A. Bahl,J. Larsen,I. Craven,P. Metherall,F. McKevitt,Caj Romanowski,N. Hoggard,D. A. Jellinek,S. Bell,E. Murray,R. Muirhead,A. James,Z. Hanzély,R. Jackson,W. Stewart,A. O'brien,A. Young,S. Shepherd,D. Cavers,L. Wallace,B. Hacking,S. Scott,D. Bowyer,Ashraf Elmahdi,Dominic G O'donovan,Azadeh Kia,Justyna M Przystal,Nastasia Nianiaris,Nicholas D Mazarakis,Paul J Mintz,Amin Hajitou,K. Karakoula,K. Phipps,W. Harkness,R. Hayward,D. Thompson,T. Jacques,B. Harding,J. Darling,T. Warr,Michael Jenkinson,L. Zhou,Emanuela Ercolano,Sylwia Ammoun,M Caroline Schmid,Magdalena Barczyk,C. O. Hanemann,F. Rowther,T. Dawson,K. Ashton,Zaynah Maherally,Kathryn E Hatherell,Karolin Kroese,P. Singh,S. McQuaid,S. Al-Rashid,K. Prise,B. Herron,E. Healy,A. Shoakazemi,M. Donnelly,R. McConnell,J. Harney,D. Conkey,E. McGrath,L. Lunsford,D. Kondziolka,A. Niranjan,H. Kano,R. Hamilton,T. Flannery,Yvonne Majani,Stuart Smith,Richard Grundy,Ruman Rahman,Sarvinder Saini,Gregory Hall,Charles Davis,T. Lawson,N. Potter,E. Goessl,Simone Wilkins,Trevor Smith,V. Petinou,I. Nicholl,J. Singh,R. Lea,P. Welsby,Inma Spiteri,Andrea Sottoriva,Nicholas Marko,Simon Tavaré,Peter Collins,Z. Su,A. Gerhard,R. Hinz,F. Roncaroli,D. Coope,K. Karabatsou,A. Sofat,J. Leggate,D. Du Plessis,F. Turkheimer,A. Jackson,K. Das,K. Herholz,Ian R Whittle,Paul Grundy,Garth Cruickshank,V. Berry,Dje Elder,N. Cohen,J. Tavaré,Georgios Zilidis,Priyanka Tibarewal,Laura Spinelli,Nick R Leslie,Sophie Green,Gemma Wall,P. Brennan,J. Baily,M. Diaz,J. Ironside,O. Sansom,V. Brunton,M. Frame,O. Thomas,L. Mohsen,V. Lupson,M. McLean,Mohit Arora,Lisa Shaw,Clare Lawrence,Jane Alder,Lavdie Rada,K. Chen,A. Shivane,D. Parkinson,Rajendra P Pangeni,M. R. Morris,Mairi MacKinnon,Aoife Williamson,Anthony Chalmers,V. Beckett,A. Joannides,R. Brock,K. McCarthy,A. Singh,H. Kardooni,N. Syed,K. Janczar,K. O'neil,C. L. Nigro,L. Lattanzio,H. Coley,E. Hatzimichael,J. Bomalaski,P. Szlosarek,T. Crook,Nicholas A Pullen,Monika Anand,Timothy Van Meter,Marjorie Boissinot,Lynette Steele,E Antonio Chiocca,Sean Lawler,Stephanie Mashal,Laura Taggart,Ellen Clarke,Ali Altinkaya,Maggie Williams,A. J. Frary,G. J. Pilkington,K. M. Prise,D. J. Coope,G. Thompson,S. J. Price,Keyoumars Ashkan,David John Coope,Konstantina Karabatsou,Amh Young,Amy J Frary,C Oliver Hanemann,Tracy J Warr,Mark R Morris,Allan James,Stephen Price,Tim Dawson,M. Morris,Shahnaz T Al Rashid,Thomas Flannery,Kevin M Prise;Suzanne Birks;Melis Altinkaya;G. Pilkington;Kathreena M Kurian;Charlene Crosby;Kirsten Hopkins;S. Williams;Laura Donovan;Amy Eason;Viktoria Bosak;Jonathon Holliday;Ivason Corbett;Melanie Keeling;Jacki Bambrough;Jane Simpson;Samantha Higgins;Harjot Dogra;Yuening Zhang;Marcus Bradley;Claudia Schmidberger;Sassan Hafizi;Imran Noorani;S. Price;Aurore Dubocq;Tomasz Jaunky;Clémence Chatelain;Luke Evans;T. Gaissmaier;Qian An;V. Hurwitz;J. Logan;R. Bhangoo;K. Ashkan;A. Gullan;R. Beaney;L. Brazil;S. Kokkinos;R. Blake;A. Singleton;Abigail Shaw;Venkat Iyer;Jennie N Jeyapalan;Isabel Cf Morley;Alfred A Hill;Muhammad A Mumin;Ruth G Tatevossian;Ibrahim Qaddoumi;David W Ellison;Denise Sheer;A. Frary;S. Jefferies;F. Harris;N. Burnet;R. Jena;C. Watts;Brian Haylock;Sophie Leow-Dyke;Nitika Rathi;Helen Wong;Julie Dunn;Atik Baborie;Daniel Crooks;David Husband;Adi Shenoy;Andrew Brodbelt;Carol Walker;A. Bahl;J. Larsen;I. Craven;P. Metherall;F. McKevitt;Caj Romanowski;N. Hoggard;D. A. Jellinek;S. Bell;E. Murray;R. Muirhead;A. James;Z. Hanzély;R. Jackson;W. Stewart;A. O'brien;A. Young;S. Shepherd;D. Cavers;L. Wallace;B. Hacking;S. Scott;D. Bowyer;Ashraf Elmahdi;Dominic G O'donovan;Azadeh Kia;Justyna M Przystal;Nastasia Nianiaris;Nicholas D Mazarakis;Paul J Mintz;Amin Hajitou;K. Karakoula;K. Phipps;W. Harkness;R. Hayward;D. Thompson;T. Jacques;B. Harding;J. Darling;T. Warr;Michael Jenkinson;L. Zhou;Emanuela Ercolano;Sylwia Ammoun;M Caroline Schmid;Magdalena Barczyk;C. O. Hanemann;F. Rowther;T. Dawson;K. Ashton;Zaynah Maherally;Kathryn E Hatherell;Karolin Kroese;P. Singh;S. McQuaid;S. Al-Rashid;K. Prise;B. Herron;E. Healy;A. Shoakazemi;M. Donnelly;R. McConnell;J. Harney;D. Conkey;E. McGrath;L. Lunsford;D. Kondziolka;A. Niranjan;H. Kano;R. Hamilton;T. Flannery;Yvonne Majani;Stuart Smith;Richard Grundy;Ruman Rahman;Sarvinder Saini;Gregory Hall;Charles Davis;T. Lawson;N. Potter;E. Goessl;Simone Wilkins;Trevor Smith;V. Petinou;I. Nicholl;J. Singh;R. Lea;P. Welsby;Inma Spiteri;Andrea Sottoriva;Nicholas Marko;Simon Tavaré;Peter Collins;Z. Su;A. Gerhard;R. Hinz;F. Roncaroli;D. Coope;K. Karabatsou;A. Sofat;J. Leggate;D. Du Plessis;F. Turkheimer;A. Jackson;K. Das;K. Herholz;Ian R Whittle;Paul Grundy;Garth Cruickshank;V. Berry;Dje Elder;N. Cohen;J. Tavaré;Georgios Zilidis;Priyanka Tibarewal;Laura Spinelli;Nick R Leslie;Sophie Green;Gemma Wall;P. Brennan;J. Baily;M. Diaz;J. Ironside;O. Sansom;V. Brunton;M. Frame;O. Thomas;L. Mohsen;V. Lupson;M. McLean;Mohit Arora;Lisa Shaw;Clare Lawrence;Jane Alder;Lavdie Rada;K. Chen;A. Shivane;D. Parkinson;Rajendra P Pangeni;M. R. Morris;Mairi MacKinnon;Aoife Williamson;Anthony Chalmers;V. Beckett;A. Joannides;R. Brock;K. McCarthy;A. Singh;H. Kardooni;N. Syed;K. Janczar;K. O'neil;C. L. Nigro;L. Lattanzio;H. Coley;E. Hatzimichael;J. Bomalaski;P. Szlosarek;T. Crook;Nicholas A Pullen;Monika Anand;Timothy Van Meter;Marjorie Boissinot;Lynette Steele;E Antonio Chiocca;Sean Lawler;Stephanie Mashal;Laura Taggart;Ellen Clarke;Ali Altinkaya;Maggie Williams;A. J. Frary;G. J. Pilkington;K. M. Prise;D. J. Coope;G. Thompson;S. J. Price;Keyoumars Ashkan;David John Coope;Konstantina Karabatsou;Amh Young;Amy J Frary;C Oliver Hanemann;Tracy J Warr;Mark R Morris;Allan James;Stephen Price;Tim Dawson;M. Morris;Shahnaz T Al Rashid;Thomas Flannery;Kevin M Prise;
Journal Neuro-Oncology
Year 2012
DOI
10.1093/neuonc/nos198
URL
https://sciprofiles.com/publication/view/a0256541d029de6c5cb4058bd750abcf
Keywords
Drug resistance glioma methylation cerebellum astrocytes lymphoma steroids cancer stem cell astrocytomas

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