10073-CBMS-6 CURCUMIN ANALOG B EXHIBIT ANTI-TUMOR ACTIVITY AGAINST GLIOBLASTOMAAT LOWER CONCENTRATIONS THAN CURCUMIN

Abstract PURPOSE Glioblastoma (GBM) has a high risk of recurrence and a poor prognosis due to the difficulty of surgical resection and resistance to the standard treatment, temozolomide. Therefore, the development of noble therapeutic agents against GBM is required. This study investigated the anti-tumor activity of the curcumin (Cur) analog Compound B (ComB) against GBM. METHODS AND RESULTS To evaluate anti-tumor activity against GBM, we performed an MTT assay. The human glioblastoma cell lines U87-MG and U251 were pre-treated with Cur or ComB, and then cell viability was examined using a cell counting kit, and IC50 values were calculated. The IC50 value for U87-MG of Cur was 9.78 μM, and that of ComB was1.28 μM. The IC50 value for U251 of Cur was 9.50 μM, and that of ComB was 0.64 μM. To examine the effects of ComB on normal cells, the same MTT assay was performed on primary cultured astrocytes prepared from neonatal rats. ComB did not reduce cell viability in astrocytes at concentrations that had an anti-tumor effect on GBM cells. Next, a cell cycle analysis was performed with Propidium Iodide (PI) staining and an apoptosis assay with Annexin V/PI staining using flow cytometry. ComB induced cell cycle G2/M arrest and apoptosis at lower concentrations than Cur. qPCR showed that mRNA expression levels of CDK1 and CyclinB1, which play an essential role in the progression from the G2 phase to the M phase, decreased by ComB at lower concentrations than Cur. DISCUSSION These results suggest that ComB, at lower concentrations than Cur, has an anti-tumor effect without affecting normal cells by inducing cell cycle arrest and apoptosis against GBM. Further detailed analysis and in vivo studies are expected to lead to the development of novel therapeutic agents for GBM.