Sodium butyrate induces colorectal cancer cell apoptosis via the MCU/Drp1 pathway

Sodium butyrate (NaB) is a short-chain fatty acid that has anti-colorectal cancer (CRC) effects. However, the underlying mechanism has not been identified. A variety of programmed cell death inhibitors were used to treat CRC HCT-116 cells with NaB alone or in combination. Cell viability was detected by MTT, and apoptosis-related protein expression of mitochondrial calcium uniporter (MCU), Drp1, Bcl-2, and cPARP were detected by PCR and Western blotting. Calcium ion content was detected by fluorescence enzyme labeling, mitochondrial calcium ion fluorescence intensity was observed by fluorescence microscopy, apoptosis morphology was observed by Hoechst staining, and apoptosis rate was detected by flow cytometry. Results showed that NaB inhibits cell activity and induces apoptosis of CRC HCT-116 cells, but has no significant effect on normal intestinal epithelial cells. In addition, NaB increased the content of calcium ions and down-regulated the expression of Drp1. BAPTA, which chelates calcium ions, reversed the down-regulation of Drp1 expression by NaB, and reduced apoptosis induced by NaB. NaB promoted the expression of MCU, and ruthenium red, an inhibitor of MCU, reversed the increase of calcium ion concentration, down-regulated the expression of Drp1, and attenuated the apoptosis induced by NaB. In vivo results confirmed that MCU and Drp1 are involved in the inhibition of the growth of human CRC xenografts in nude mice by NaB. NaB induces apoptosis in CRC cells through the MCU/Drp1 pathway, which provides a new prospect for the application of NaB in the treatment of CRC.