10051-CBMS-4 CURCUMIN ANALOG COMPOUND A INHIBITS THE GROWTH OF GLIOBLASTOMA BY INDUCING G2/M PHASE ARREST AND APOPTOSIS AT A LOWER CONCENTRATION THAN CURCUMIN

Abstract

Abstract PURPOSE Glioblastoma (GBM) is the most common and aggressive primary brain tumor. Over 15,000 patients are diagnosed with GBM yearly, with a median survival expectancy of<15 months and<10% survival rate beyond five years, despite applying conventional multimodal treatment containing surgical resection, chemotherapy, and radiation therapy. The efficiency of conventional therapies is limited due to the lack of specificity and the accuracy of eradicating aggressive diffusing GBM cells. Developing new therapeutic agents against GBM is strongly recommended. The purpose of this study was to investigate whether the curcumin (Cur) analogs Compound A (ComA) possess anti-tumor activity against GBM. METHODS AND RESULTS To evaluate the anti-tumor activity of ComA against GBM, we performed an MTT assay. The human GBM cell lines U87-MG and U251 were pre-treated with Cur or ComA, cell viability was examined using a cell counting kit, and then IC50 values were evaluated. The IC50 values for U87-MG were: Cur, 9.78 μM; ComA, 2.42 μM. Those for U251 were: Cur, 9.50 μM; ComA, 2.27 μM. To examine the effects of ComA on normal cells, the same MTT assay was performed on primary cultured astrocytes from neonatal rats. ComA did not significantly reduce the cell viability in astrocytes at concentrations that had an anti-tumor effect on GBM cells (ComA, 3 μM). Next, a cell cycle analysis was performed with PI staining and an apoptosis assay with Annexin V/PI staining using flowcytometry. ComA, at lower concentrations than Cur, induced G2/M phase arrest and apoptosis. qPCR showed that ComA decreases CDK1 and CyclinB1 mRNA levels, the cell cycle-related proteins, at a lower concentration than Cur. DISCUSSION These results indicate that ComA has an anti-tumor effect by inducing cell cycle arrest and apoptosis against GBM at lower concentrations than Cur.