10096- CBMS-3 CURCUMIN ANALOGUE A SHOWS ANTI-TUMOR EFFECTS AT LOWER CONCENTRATIONS THAN CURCUMIN IN GLIOBLASTOMA CELLS

Abstract PURPOSE Curcumin (Cur), a natural compound, possesses antitumor activity against glioblastoma cells (GBM). However, the bioavailability of Cur is too low to exhibit beneficial effects in vivo. We hypothesized that Cur analogues with enhanced anti-tumor activity against GBM could increase bioavailability and effectiveness. This study investigated the anti-tumor activity of a Cur analog, Compound A (ComA), against GBM. METHODS AND RESULTS To evaluate the anti-tumor activity of ComA against GBM, an MTT assay was performed. Human GBM cell lines U251 and T98G were pre-treated with Cur or ComA, and then cell viability was examined using a CCK-8 kit. The IC50 values for U251 were 10.9 μM (Cur) and 2.9 μM (ComA), and those for T98G were 16.6 μM (Cur) and 4.7 μM (ComA). To examine the effects of Cur and ComA on non-tumor 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 had an anti-tumor effect on GBM cells. Next, a cell cycle analysis was performed on U251 and T98G cells using flow cytometry with PI staining. ComA induced G2/M phase arrest at lower concentrations than Cur. Furthermore, the amount of cellular uptake of Cur and ComA in these cells was quantified. Cellular uptake of ComA was 3.8 times higher than Cur in U251 cells and 3.5 times higher in T98G cells. Finally, when mice were orally administrated with Cur or ComA, the maximum plasma concentration of ComA was about 30 times higher than that of Cur. DISCUSSION These results suggest that ComA has an anti-tumor effect due to cell cycle arrest against GBM that occurs at lower concentrations than Cur. Further in vivo studies are required to develop ComA-based novel therapeutic agents against GBM.