CSIG-15. CURCUMIN ANALOG INDUCES G2/M ARREST IN HUMAN GLIOBLASTOMA CELLS AT LOWER CONCENTRATIONS THAN CURCUMIN DUE TO ITS HIGHER CELLULAR UPTAKE

Abstract PURPOSE Glioblastoma (GBM) has a high risk of recurrence and a poor prognosis. Curcumin (Cur), a natural compound, possesses inhibitory potentials for glioblastoma cells. However, the absorption efficacy of Curcumin is too low to exhibit beneficial effects in vivo. Thus, Curcumin analog with higher anti-tumor efficacy against GBM can be novel therapeutic agent. This study investigated the anti-tumor activity of the Curcumin analog Compound A (ComA) against GBM. METHODS AND RESULTS To evaluate anti-tumor activity of ComA against GBM, we performed a MTT assay. The human glioblastoma cell lines U251 and T98G were pre-treated with Cur or ComA, then cell viability was examined using a CCK-8 kit, and IC50 values were calculated. The IC50 values for U251 were: Cur, 10.9 µM; ComA, 2.9 µM.[MOU1] Those for T98G were: Cur, 16.6 µM; ComA, 4.7 µM[MOU2]. To examine the effects of Cur and ComA on normal cells, the same MTT assay was performed on primary cultured astrocytes from neonatal rats. Neither Cur nor ComA resulted in reduced cell viability in astrocytes at concentrations that had an anti-tumor effect on GBM cells (Cur, 16.6 µM; ComA, 4.7 µM). Next, a cell cycle analysis was performed with PI staining using flow cytometry for U251 and T98G. ComA induced G2/M phase arrest at lower concentrations than Cur. Finally, the amount of cellular uptake of Cur and ComA were quantitated in U251 and T98G. Cellular uptake of ComA was high compared with that of Cur (U251, 3.8 times; T98G, 3.5 times).[MOU3] DISCUSSION These results suggest that ComA have an anti-tumor effect by inducing cell cycle arrest against GBM at lower concentrations than Cur, due to its higher cellular uptake than Cur. Further detailed analysis and in vivo studies are expected to lead to the development of novel therapeutic agents for GBM.