Genistein potentiated the cytotoxic effect of entinostat in colorectal cancer cell lines.

Abstract

Background and purpose: Colorectal cancer (CRC) is the second leading cause of cancer death. While surgery and medicines offer complete treatment, recurrence and medication resistance pose challenges. This study assessed the cytotoxic impact of entinostat, a histone deacetylase (HDAC) inhibitor, and genistein, a soybean isoflavone, combination on CRC cells.

Experimental approach: The cytotoxic effect of genistein, combined with entinostat, was tested in HCT-116 and HT-29 cell lines, along with their impact on migration and colony formation. Gene expression of the cell cycle regulatory protein CDC25A was assessed using qPCR.

Findings/results: The IC50 values of genistein, entinostat, and their combination in HCT-116 cells were 24.48 μM, 13.65 μM, and 14.55 μM, respectively. In HT-29, the IC50 values were 30.41 μM, 20.25 μM, and 19.98 μM, respectively. In the HT-29 cell line, a 1:1 ratio of entinostat and genistein resulted in a combination index of 0.6 using a concentration of 1.56 μM of each compound, indicating a synergistic effect. In contrast, no synergistic effect was produced between the two drugs in the HCT-116 cell line. In HCT-116 cells, genistein, entinostat, and their combination significantly reduced wound closure compared to the control. In contrast, in HT-29 cells, only the combination treatment was effective, while genistein and entinostat alone showed no notable impact. In HCT-116, entinostat, genistein, and their combination reduced the number of colonies significantly compared to the control, while in HT-29, only entinostat and the combination reduced the number of colonies significantly compared to the control. Furthermore, the combination of genistein with entinostat was more effective in reducing CDC25A expression in the HT-29 cells compared to entinostat treatment alone.

Conclusions and implications: Combining genistein with entinostat could potentiate the entinostat cytotoxic effect in CRC.