10296- CBMS-8 CURCUMIN, AN INHIBITOR OF P300-HAT ACTIVITY, SUPPRESSED GLIOBLASTOMA CELL PROLIFERATION IN A STRUCTURE-ACTIVITY RELATIONSHIP STUDY

Abstract PURPOSE Glioblastoma (GBM) is the most common malignant brain tumor. In the treatment of GBM, it is difficult to completely remove tumor tissue by surgery alone, and radiotherapy and chemotherapy are typically used to treat the remaining tissue. However, GBM has a very poor prognosis, with a 5-year survival rate of approximately 10%. In recent years, molecular targeted therapies are becoming more common for all types of cancer, and histone acetylase (HAT) activity has attracted attention as a potential therapeutic target. It has been reported that the HAT activity of the transcriptional co-activator p300 plays a key role in the progression of pancreatic cancer. However, it is not clear whether p300-HAT activity is also crucial for the growth of GBM cells. METHODS AND RESULTS We previously reported that while the natural compound curcumin (Cur) inhibits p300-HAT activity, the Cur derivative GO-Y041 does not. To assess the role of p300-HAT activity in GBM cell proliferation, we compared the effect of Cur and GO-Y041 on the cells with an MTT assay. The human GBM cell line U87MG was treated with the two compounds, and cell viability was examined using CCK-8 kit. The results showed that the viability of the cells was significantly decreased by 10 μM Cur compared to the untreated group, while no decrease in viability was observed with 10 μM GO-Y041. DISCUSSION These results suggest that p300-HAT activity may play an important role in the proliferation of GBM cells. However, as Cur also acts on proteins other than p300, it is still not completely clear whether p300-HAT activity is essential for GBM growth. To provide insights into the role of p300-HAT activity in GBM cell growth, we will generate cells in which p300-HAT activity alone can be abolished using genetic engineering techniques to pursue the development of novel GBM therapies.