The present study provides groundbreaking evidence that CUR inhibited colon cancer development via the upregulation of the TSGs ARHGEF12 and APAF1. Furthermore, we performed molecular docking and demonstrated that the curcumin can form a stable H-bond with ARHGEF12 and RhoA, respectively, indicating curcumin can bind tightly to these two proteins (Xiang et al., 2022; He et al., 2023), as shown in the schematic diagram (Figure 6, 7, by Figdraw). Here, ARHGEF12 is linked to colonic neoplasm.