TDH-11 inhibits the proliferation and colonization of colorectal cancer by reducing the activity of HDAC.

Histone deacetylase inhibitors (HDACIs) have demonstrated significant efficacy and minimal toxic side effects in certain hematological tumors. Nevertheless, their utilization in the therapy of solid tumors, including colorectal cancer (CRC), is constrained by the occurrence of adverse effects such as myelosuppression and cardiotoxicity. Therefore, the development of more efficient and safer HDACIs is crucial for managing CRC. Here, the effects of TDH-11 (a novel HDAC inhibitor) and the underlying molecular mechanisms that inhibits the deveolpment and progression of CRC cells were investigated using in vitro and in vivo experiments. The results indicated that TDH-11 inhibited CRC tumorigenic behavior while also promoted apoptosis and cell cycle arrest. In vivo, TDH-11 markedly inhibited tumor progression and reduces tumor colonization without causing substantial damage to key organs, such as the kidneys, heart, lungs, spleen, and liver. Results of RNA sequencing and western blot suggested that TDH-11 exerted its antitumor effects through modulation of the p53 signaling pathway and its downstream pathways involved in apoptosis and cell cycle regulation. In summary, TDH-11 exhibited significant potential in suppressing the growth and colonization of CRC, as determined in both cellular and animal models. These results provided novel insights into CRC-associated pathways and suggest promising prospects for managing advanced and metastatic CRC.