Related Experiment Video
Updated: Jun 16, 2025
Author Spotlight: Liujunzi Decoction as a Traditional Chinese Treatment for Coloproctitis Cancer
Published on: October 13, 2023
Sodium butyrate induces colorectal cancer cell apoptosis via the MCU/Drp1 pathway
Yong Qin1, Lulin Liu1, Shaofeng Luo1
1Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Abstract:
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.
Insights
Sodium butyrate (NaB) induces colorectal cancer (CRC) cell apoptosis via the mitochondrial calcium uniporter (MCU)/Drp1 pathway. This discovery offers new therapeutic avenues for CRC treatment.
Area of Science:
- Oncology
- Molecular Biology
- Cell Biology
Background:
- Sodium butyrate (NaB), a short-chain fatty acid, exhibits anti-colorectal cancer (CRC) properties.
- The precise molecular mechanisms underlying NaB's anti-CRC effects remain largely unidentified.
- Understanding these mechanisms is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To elucidate the mechanism by which NaB inhibits CRC cell growth and induces apoptosis.
- To investigate the role of calcium ions and mitochondrial dynamics in NaB-mediated CRC cell death.
- To explore the involvement of the mitochondrial calcium uniporter (MCU) and Drp1 in NaB's anti-cancer effects.
Main Methods:
- CRC HCT-116 cells were treated with NaB, alone or with apoptosis inhibitors.
- Cell viability (MTT assay), apoptosis markers (Western blotting, flow cytometry), calcium ion levels (fluorescence assays), and mitochondrial morphology were assessed.
- Protein expression of MCU and Drp1 was analyzed via PCR and Western blotting.
- In vivo studies utilized human CRC xenografts in nude mice.
Main Results:
- NaB significantly inhibited CRC HCT-116 cell activity and induced apoptosis, with no effect on normal cells.
- NaB increased intracellular calcium ion content and down-regulated Drp1 expression.
- Inhibition of MCU or chelation of calcium ions reversed NaB-induced Drp1 down-regulation and attenuated apoptosis.
- In vivo experiments confirmed MCU and Drp1 involvement in NaB's inhibition of CRC xenograft growth.
Conclusions:
- NaB induces apoptosis in CRC cells through the MCU/Drp1 pathway.
- This pathway involves increased calcium ion influx mediated by MCU, leading to Drp1 modulation.
- NaB represents a promising therapeutic agent for CRC, targeting the MCU/Drp1-mediated apoptotic pathway.
