ArticleFrontiers in cell and developmental biology2021
Short-Chain Fatty Acid Butyrate Induces Cilia Formation and Potentiates the Effects of HDAC6 Inhibitors in Cholangiocarcinoma Cells.
Article in Frontiers in cell and developmental biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Butyrate and Butyrate-Producing Bacteria in Cardiovascular-Kidney-Metabolic Syndrome.Antioxidants (Basel, Switzerland) · 2026Review
- Blood and tissue dysregulated bile acids and short-chain fatty acids in cholangiocarcinoma.JHEP reports : innovation in hepatology · 2025Article
- Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.Seminars in liver disease · 2025Review
- Cholangiocyte ciliary defects induce sustained epidermal growth factor receptor signaling.Hepatology (Baltimore, Md.) · 2025Article
- Reprogramming of fatty acid metabolism: a hidden force regulating the occurrence and progression of cholangiocarcinoma.Cell death discovery · 2025Review
- Dual Roles of Canagliflozin on Cholangiocarcinoma Cell Growth and Enhanced Growth Suppression in Combination with FK866.International journal of molecular sciences · 2025Article
- Applications of 3D models in cholangiocarcinoma.Frontiers in oncology · 2025Review
- Targeting lipogenesis promotes the synergistic effect of the selective HDAC6 inhibitor ITF3756 with bortezomib in colon cancer cells.Frontiers in pharmacology · 2025Article
- NAMPT Overexpression Drives Cell Growth in Polycystic Liver Disease through Mitochondrial Metabolism Regulation.The American journal of pathology · 2024Article
- Review
- Whole-exome sequencing reveals novel cancer genes and actionable targets in biliary tract cancers in primary sclerosing cholangitis.Hepatology communications · 2024Article
- A MiR181/Sirtuin1 regulatory circuit modulates drug response in biliary cancers.Clinical and experimental medicine · 2024Article
- The Role of Gut Microbiome-Derived Short-Chain Fatty Acid Butyrate in Hepatobiliary Diseases.The American journal of pathology · 2023Review
- The NAMPT Inhibitor FK866 in Combination with Cisplatin Reduces Cholangiocarcinoma Cells Growth.Cells · 2023Article
- Gut microbiota-derived short-chain fatty acids regulate gastrointestinal tumor immunity: a novel therapeutic strategy?Frontiers in immunology · 2023Review
- Short-chain fatty acids ameliorate necrotizing enterocolitis-like intestinal injury through enhancing Notch1-mediated single immunoglobulin interleukin-1-related receptor, toll-interacting protein, and A20 induction.American journal of physiology. Gastrointestinal and liver physiology · 2023Article
- Targeting HDAC6 to Overcome Autophagy-Promoted Anti-Cancer Drug Resistance.International journal of molecular sciences · 2022Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Cholangiocarcinoma (CCA) is a deadly form of liver cancer with limited therapeutic approaches. The pathogenesis of CCA involves the loss of primary cilia in cholangiocytes, an important organelle that regulates several key cellular functions including the regulation of cell polarity, growth, and differentiation, by a mechanism involving increased expression of deacetylases like HDAC6 and SIRT1. Therefore, cilia restoration may represent an alternative and novel therapeutic approach against CCA. Butyrate is produced by bacterial fermentation of fibers in the intestine and has been shown to inhibit SIRT1, showing antitumor effects on various cancers. Herein, we investigated the role of butyrate on CCA cell proliferation, migration, and EMT and evaluated the synergistic effects with specific HDAC6 inhibition. When CCA cells, including HuCCT1 and KMCH, were treated with butyrate, the cilia formation and acetylated-tubulin levels were increased, while no significant effects were observed in normal human cholangiocytes. Butyrate treatment also depicted reduced cell proliferation in HuCCT1 and KMCH cells, but on the other hand, it affected cell growth of the normal cholangiocytes only at high concentrations. In HuCCT1 cells, spheroid formation and cell migration were also halted by butyrate treatment. Furthermore, we found that butyrate augmented the previously described effects of HDAC6 inhibitors on CCA cell proliferation and migration by reducing the expression of CD44, cyclin D1, PCNA, Zeb1, and Vimentin. In summary, butyrate targets cancer cell growth and migration and enhances the anti-cancer effects of HDAC6 inhibitors in CCA cells, suggesting that butyrate may have therapeutic effects in CCA and other ciliopathies.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.