Abstracts from the 2012 BNOS Conference

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.