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Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1
Wenqi Wang1,2, Daoquan Fang3, Hao Zhang1
1Department of Microbiology and Immunology, School of Laboratory Medicine, Wenzhou Medical University, Wenzhou 325000, People's Republic of China.
Background:
Sodium butyrate (NaB) is a short-chain fatty acid which is produced by bacterial fermentation of nondigestible dietary fiber and has been reported to exert anti-tumor effects in many tumors including colorectal cancer (CRC). However, the role of thioredoxin-1 (Trx-1) in NaB-induced anti-tumor effect has not been completely clarified.
Materials And Methods:
Effects of NaB on the growth of CRC cell lines HT29 and SW480 were detected by the Cell Counting Kit-8 (CCK-8) and colony formation assays. The apoptotic cells were determined by flow cytometry, and cell migration was assessed by a Transwell assay. Western blot analysis was used to test the Trx-1 and epithelial-to-mesenchymal transition (EMT)-related proteins level. Reactive oxygen species (ROS) level was determined and N-acetylcysteine (NAC) recovery experiment was performed in CRC cells. In addition, mice xenograft model was established to test the effect of NaB on CRC growth in vivo. Further, the effects of NaB on CRC cells with overexpression or knockdown were tested by the CCK-8 and Transwell assays.
Results:
NaB treatment significantly inhibited cell growth and decreased Trx-1 protein expression in CRC cells but not in normal colon epithelial cells. NaB also induced apoptosis, inhibited colony formation, migration and EMT in CRC cells. Besides, NaB increased ROS level in CRC cells and NAC reversed NaB-induced inhibition of cell proliferation. Moreover, downregulation of Trx-1 significantly enhanced NaB-induced inhibitory effects on cell growth and migration, whereas overexpression of Trx-1 attenuated NaB-induced inhibitory effects on growth and migration in CRC cells.
Conclusion:
These findings indicate that the NaB-mediated anti-tumor effects on CRC cells are related to downregulation of Trx-1.
Insights
Sodium butyrate (NaB) inhibits colorectal cancer (CRC) growth by decreasing thioredoxin-1 (Trx-1) expression. Downregulating Trx-1 enhances NaB's anti-tumor effects, indicating Trx-1's crucial role in NaB's efficacy against CRC.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Sodium butyrate (NaB), a short-chain fatty acid from dietary fiber fermentation, exhibits anti-tumor properties in various cancers, including colorectal cancer (CRC).
- The precise mechanism by which NaB exerts its anti-tumor effects, particularly the involvement of thioredoxin-1 (Trx-1), remains incompletely understood in CRC.
Purpose of the Study:
- To investigate the role of thioredoxin-1 (Trx-1) in the anti-tumor effects of sodium butyrate (NaB) on colorectal cancer (CRC) cells.
- To elucidate the molecular mechanisms underlying NaB-induced growth inhibition, apoptosis, and migration in CRC.
Main Methods:
- Cell Counting Kit-8 and colony formation assays were used to assess cell viability and proliferation.
- Flow cytometry and Transwell assays evaluated apoptosis and cell migration, respectively.
- Western blotting, reactive oxygen species (ROS) measurement, and in vivo xenograft models were employed to analyze Trx-1 expression, ROS levels, and tumor growth.
Main Results:
- NaB significantly inhibited CRC cell growth, induced apoptosis, and suppressed migration and epithelial-to-mesenchymal transition (EMT).
- NaB treatment led to decreased Trx-1 protein expression and increased ROS levels in CRC cells.
- Downregulation of Trx-1 potentiated NaB's anti-tumor effects, while Trx-1 overexpression attenuated them.
Conclusions:
- The anti-tumor effects of NaB in colorectal cancer are significantly associated with the downregulation of thioredoxin-1 (Trx-1).
- Targeting Trx-1 may represent a promising strategy to enhance the efficacy of NaB as an anti-cancer therapeutic for CRC.
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