Sodium Butyrate Selectively Kills Cancer Cells and Inhibits Migration in Colorectal Cancer by Targeting Thioredoxin-1
Received 22 October 2019
Accepted for publication 7 May 2020
Published 27 May 2020 Volume 2020:13 Pages 4691—4704
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Jianmin Xu
Wenqi Wang,1,2,* Daoquan Fang,3,* Hao Zhang,1 Jiao Xue,1 Drugyel Wangchuk,4 Jimei Du,1 Lei Jiang3
1Department of Microbiology and Immunology, School of Laboratory Medicine, Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 2Department of Laboratory Medicine, Shanghai University of Medicine & Health Sciences affiliated Zhoupu Hospital, Shanghai 201318, People’s Republic of China; 3Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China; 4Department of General Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Lei Jiang
Central Laboratory, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang, People’s Republic of China
Department 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.
Keywords: anti-tumor effects, colorectal cancer, short-chain fatty acid, sodium butyrate, thioredoxin-1
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