Abstract
Colorectal cancer is still a major health problem worldwide. Based on the most recent released data by the World Health Organization GLOBOCAN in 2012, colorectal cancer is the third most prevalent type of cancer in males and the second in females. In 1999, it was published the first report showing evidence of a strong correlation between diet and cancer incidence, being its positive or negative impact intimately linked to dietary patterns. A diet rich in fiber is associated with a low risk of developing colorectal cancer. The fermentation of the dietary fiber by intestinal microflora results in production of butyrate, which plays a plurifunctional role on the colonocytes, and it has also been reported as a chemopreventive agent. However, there are limited studies focusing its anti-cancer potential. Here, we review the recent new insights that focus butyrate and its role in colorectal cancer prevention and treatment, from its synthesis, metabolism, and transport, through its involvement on several cancer-related signaling pathways, to the novel existing approaches for its clinical use.
This is a preview of subscription content, access via your institution.




References
Knudsen, B. K. E., Serena, A., Canibe, N., & Juntunen, K. S. (2003). New insight into butyrate metabolism. Proceedings of the Nutrition Society, 62, 81–86.
Vital, M., Howe, A. C., & Tiedje, J. M. (2014). Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. mBio, 5(2), 1–11. doi:10.1128/mBio.00889-14.
Mortensen, P. B., & Clausen, M. R. (1996). Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scandinavian Journal of Gastroenterology. Supplement, 216, 132–148.
Daly, K., Cuff, M. A., Fung, F., & Shirazi-Beechey, S. P. (2005). The importance of colonic butyrate transport to the regulation of genes associated with colonic tissue homoeostasis. Biochemical Society Transactions, 33, 733–735. doi:10.1042/BST0330733.
Hamer, H. M., Jonkers, D., Venema, K., Vanhoutvin, S., Troost, F. J., & Brummer, R.-J. (2008). Review article: the role of butyrate on colonic function. Alimentary Pharmacology & Therapeutics, 27(2), 104–119. doi:10.1111/j.1365-2036.2007.03562.x.
Ahmad, M. S., Krishnan, S., Ramakrishna, B. S., Mathan, M., Pulimood, A. B., & Murthy, S. N. (2000). Butyrate and glucose metabolism by colonocytes in experimental colitis in mice. Gut, 46(4), 493–499.
Topping, D. L., & Clifton, P. M. (2001). Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiological Reviews, 81(3), 1031–1064. doi:10.1002/(SICI)1096-8644(199706)103:2<157::AID-AJPA2>3.0.CO;2-R.
Louis, P., & Flint, H. J. (2009). Diversity, metabolism and microbial ecology of butyrate-producing bacteria from the human large intestine. FEMS Microbiology Letters, 294(1), 1–8. doi:10.1111/j.1574-6968.2009.01514.x.
Pryde, S. E., Duncan, S. H., Hold, G. L., Stewart, C. S., & Flint, H. J. (2002). The microbiology of butyrate formation in the human colon. FEMS Microbiology Letters, 217, 133–139. doi:10.1016/S0378-1097(02)01106-0.
Genz, A., Engelhardt, W., & Busche, R. (1999). Maintenance and regulation of the pH microclimate at the luminal surface of the distal colon of guinea-pig. 507–519.
Sehested, J., Diernaes, L., Moller, P. D., & Skadhauge, E. (1996). Transport of sodium across the isolated bovine rumen epithelium: interaction with short-chain fatty acids, chloride and bicarbonate. Experimental Physiology, 81, 79–94.
Gonçalves, P., & Martel, F. (2013). Butyrate and colorectal cancer: the role of butyrate transport. Current Drug Metabolism, 14(9), 994–1008. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/24160296.
Cuff, M. A., & Shirazi-Beechey, S. P. (2004). The importance of butyrate transport to the regulation of gene expression in the colonic epithelium. Biochemical Society Transactions, 32, 1100–1102. doi:10.1042/BST0321100.
Glade, M. J. (1999). Food, nutrition, and the prevention of cancer: a global perspective. Nutrition, 15(6), 523–526.
Baena Ruiz, R., & Salinas Hernández, P. (2014). Diet and cancer: risk factors and epidemiological evidence. Maturitas, 77(3), 202–208. doi:10.1016/j.maturitas.2013.11.010.
Anand, P., Kunnumakkara, A. B., Kunnumakara, A. B., Sundaram, C., Harikumar, K. B., Tharakan, S. T., … & Aggarwal, B. B. (2008). Cancer is a preventable disease that requires major lifestyle changes. Pharmaceutical Research, 25(9), 2097–116. doi:10.1007/s11095-008-9661-9.
Scharlau, D., Borowicki, A., Habermann, N., Hofmann, T., Klenow, S., Miene, C., … & Glei, M. (2009). Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutation Research, 682(1), 39–53. doi:10.1016/j.mrrev.2009.04.001.
Zeng, H., Lazarova, D. L., & Bordonaro, M. (2014). Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention. World Journal of Gastrointestinal Oncology, 6(2), 41–51. doi:10.4251/wjgo.v6.i2.41.
Irigaray, P., Newby, J. A., Clapp, R., Hardell, L., Howard, V., Montagnier, L., … & Belpomme, D. (2007). Lifestyle-related factors and environmental agents causing cancer: an overview. Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie, 61(10), 640–58. doi:10.1016/j.biopha.2007.10.006.
Pericleous, M., Mandair, D., & Caplin, M. E. (2013). Diet and supplements and their impact on colorectal cancer. Journal of Gastrointestinal Oncology, 4(4), 409–423. doi:10.3978/j.issn.2078-6891.2013.003.
Durko, L., & Malecka-Panas, E. (2014). Lifestyle modifications and colorectal cancer. Current Colorectal Cancer Reports, 10, 45–54. doi:10.1007/s11888-013-0203-4.
Bultman, S. J. (2014). Molecular pathways: gene-environment interactions regulating dietary fiber induction of proliferation and apoptosis via butyrate for cancer prevention. Clinical Cancer Research: An Official Journal of the American Association for Cancer Research, 20(4), 799–803. doi:10.1158/1078-0432.CCR-13-2483.
Leonel, A. J., & Alvarez-Leite, J. I. (2012). Butyrate: implications for intestinal function. Current Opinion in Clinical Nutrition and Metabolic Care, 15(5), 474–479. doi:10.1097/MCO.0b013e32835665fa.
Fung, K. Y. C., Cosgrove, L., Lockett, T., Head, R., & Topping, D. L. (2012). A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate. The British Journal of Nutrition, 108(5), 820–831. doi:10.1017/S0007114512001948.
Lupton, J. R. (2004). Microbial degradation products influence colon cancer risk: the butyrate controversy. The Journal of Nutrition, 134, 479–482.
Klampfer, L., Huang, J., Sasazuki, T., Shirasawa, S., & Augenlicht, L. (2003). Inhibition of interferon; signaling by the short chain fatty acid butyrate. Molecular Cancer Research, 1(September), 855–862.
Scholz, D. (2011). The role of nutrition in the etiology of inflammatory bowel disease. Current Problems in Pediatric and Adolescent Health Care, 41(9), 248–253. doi:10.1016/j.cppeds.2011.04.005.
Rogler, G. (2014). Chronic ulcerative colitis and colorectal cancer. Cancer Letters, 345(2), 235–241. doi:10.1016/j.canlet.2013.07.032.
Wang, K., & Karin, M. (2013). Common flora and intestine: a carcinogenic marriage. Cellular Logistics, 3(1), e24975. doi:10.4161/cl.24975.
Peng, L., Li, Z.-R., Green, R. S., Holzman, I. R., & Lin, J. (2009). Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers. The Journal of Nutrition, 139(9), 1619–1625. doi:10.3945/jn.109.104638.
Renaud, F., Vincent, A., Mariette, C., Crépin, M., Stechly, L., Truant, S., … & Buisine, M.-P. (2014). MUC5AC hypomethylation is a predictor of microsatellite instability independently of clinical factors associated with colorectal cancer. International Journal of Cancer. Journal International du Cancer, 00. doi:10.1002/ijc.29342.
Hatayama, H., Iwashita, J., Kuwajima, A., & Abe, T. (2007). The short chain fatty acid, butyrate, stimulates MUC2 mucin production in the human colon cancer cell line, LS174T. Biochemical and Biophysical Research Communications, 356(3), 599–603. doi:10.1016/j.bbrc.2007.03.025.
Blum, H. E. (1995). Colorectal cancer: future population screening for early colorectal cancer. European Journal of Cancer (Oxford, England : 1990), 31A(7-8), 1369–1372.
Canani, R. B., Costanzo, M. D., Leone, L., Pedata, M., Meli, R., & Calignano, A. (2011). Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World Journal of Gastroenterology: WJG, 17(12), 1519–1528. doi:10.3748/wjg.v17.i12. 1519.
Soret, R., Chevalier, J., De Coppet, P., Poupeau, G., Derkinderen, P., Segain, J. P., & Neunlist, M. (2010). Short-chain fatty acids regulate the enteric neurons and control gastrointestinal motility in rats. Gastroenterology, 138(5), 1772–1782. doi:10.1053/j.gastro.2010.01.053.
Hurst, N. R., Kendig, D. M., Murthy, K. S., & Grider, J. R. (2014). The short chain fatty acids, butyrate and propionate, have differential effects on the motility of the guinea pig colon. Neurogastroenterology and Motility: The Official Journal of the European Gastrointestinal Motility Society, 26(11), 1586–1596. doi:10.1111/nmo.12425.
Kautenburger, T., Beyer-Sehlmeyer, G., Festag, G., Haag, N., Kühler, S., Küchler, A., & … Pool-Zobel, B. L. (2005). The gut fermentation product butyrate, a chemopreventive agent, suppresses glutathione S-transferase theta (hGSTT1) and cell growth more in human colon adenoma (LT97) than tumor (HT29) cells. Journal of Cancer Research and Clinical Oncology, 131(10), 692–700. doi:10.1007/s00432-005-0013-4.
Scharmach, E., Hessel, S., Niemann, B., & Lampen, A. (2009). Glutathione S-transferase expression and isoenzyme composition during cell differentiation of Caco-2 cells. Toxicology, 265(3), 122–126. doi:10.1016/j.tox.2009.09.017.
Sauer, J., Richter, K. K., & Pool-Zobel, B. L. (2007). Products formed during fermentation of the prebiotic inulin with human gut flora enhance expression of biotransformation genes in human primary colon cells. The British Journal of Nutrition, 97(5), 928–937. doi:10.1017/S0007114507666422.
Hofmanová, J., Straková, N., Vaculová, A. H., Tylichová, Z., Safaříková, B., Skender, B., & Kozubík, A. (2014). Interaction of dietary fatty acids with tumour necrosis factor family cytokines during colon inflammation and cancer. Mediators of Inflammation, 2014, 848632. doi:10.1155/2014/848632.
Machiels, K., Joossens, M., Sabino, J., De Preter, V., Arijs, I., Eeckhaut, V., … & Vermeire, S. (2014). A decrease of the butyrate-producing species Roseburia hominis and Faecalibacterium prausnitzii defines dysbiosis in patients with ulcerative colitis. Gut, 63(8), 1275–83. doi:10.1136/gutjnl-2013-304833.
Chang, P. V., Hao, L., Offermanns, S., & Medzhitov, R. (2014). The microbial metabolite butyrate regulates intestinal macrophage function via histone deacetylase inhibition. Proceedings of the National Academy of Sciences of the United States of America, 111(6), 2247–2252. doi:10.1073/pnas.1322269111.
Russo, I., Luciani, A., De Cicco, P., Troncone, E., & Ciacci, C. (2012). Butyrate attenuates lipopolysaccharide-induced inflammation in intestinal cells and Crohn’s mucosa through modulation of antioxidant defense machinery. PloS One, 7(3), e32841. doi:10.1371/journal.pone.0032841.
Vieira, E. L. M., Leonel, A. J., Sad, A. P., Beltrão, N. R. M., Costa, T. F., Ferreira, T. M. R., … & Alvarez-Leite, J. I. (2012). Oral administration of sodium butyrate attenuates inflammation and mucosal lesion in experimental acute ulcerative colitis. The Journal of Nutritional Biochemistry, 23(5), 430–6. doi:10.1016/j.jnutbio.2011.01.007.
Liu, T., Li, J., Liu, Y., Xiao, N., Suo, H., Xie, K., … & Wu, C. (2012). Short-chain fatty acids suppress lipopolysaccharide-induced production of nitric oxide and proinflammatory cytokines through inhibition of NF-κB pathway in RAW264.7 cells. Inflammation, 35(5), 1676–84. doi:10.1007/s10753-012-9484-z.
Ohira, H., Fujioka, Y., Katagiri, C., Mamoto, R., Aoyama-Ishikawa, M., Amako, K., … & Ikeda, M. (2013). Butyrate attenuates inflammation and lipolysis generated by the interaction of adipocytes and macrophages. Journal of Atherosclerosis and Thrombosis, 425–442. doi:10.5551/jat.15065.
Hanahan, D., & Weinberg, R. A. (2011). Hallmarks of cancer: the next generation. Cell, 144(5), 646–674. doi:10.1016/j.cell.2011.02.013.
Donohoe, D. R., Collins, L. B., Wali, A., Bigler, R., Sun, W., & Bultman, S. J. (2012). The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Molecular Cell, 48(4), 612–626. doi:10.1016/j.molcel.2012.08.033.
Pajak, B., Orzechowski, A., & Gajkowska, B. (2007). Molecular basis of sodium butyrate-dependent proapoptotic activity in cancer cells. Advances in Medical Sciences, 52, 83–8. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/18217395.
Pan, M.-H., Lai, C.-S., Wu, J.-C., & Ho, C.-T. (2011). Molecular mechanisms for chemoprevention of colorectal cancer by natural dietary compounds. Molecular Nutrition & Food Research, 55(1), 32–45. doi:10.1002/mnfr.201000412.
Stiborová, M., Eckschlager, T., Poljaková, J., Hraběta, J., Adam, V., Kizek, R., & Frei, E. (2012). The synergistic effects of DNA-targeted chemotherapeutics and histone deacetylase inhibitors as therapeutic strategies for cancer treatment. Current Medicinal Chemistry, 19(25), 4218–38. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/22680633.
Witt, O., Deubzer, H. E., Milde, T., & Oehme, I. (2009). HDAC family: what are the cancer relevant targets? Cancer Letters, 277(1), 8–21. doi:10.1016/j.canlet.2008.08.016.
Godman, C. A, Joshi, R., Tierney, B. R., Greenspan, E., Rasmussen, T. P., Wang, H.-W., … & Giardina, C. (2008). HDAC3 impacts multiple oncogenic pathways in colon cancer cells with effects on Wnt and vitamin D signaling. Cancer Biology and Therapy, 7(10), 1570–80. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2614677&tool=pmcentrez&rendertype=abstract.
Li, Y., Zhang, X., Polakiewicz, R. D., Yao, T.-P., & Comb, M. J. (2008). HDAC6 is required for epidermal growth factor-induced beta-catenin nuclear localization. The Journal of Biological Chemistry, 283(19), 12686–12690. doi:10.1074/jbc.C700185200.
Ma, X., Ezzeldin, H. H., & Diasio, R. B. (2009). Histone deacetylase inhibitors: current status and overview of recent clinical trials. Drugs, 69(14), 1911–1934. doi:10.2165/11315680-000000000-00000.
Minucci, S., & Pelicci, P. G. (2006). Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer. Nature Review. Cancer, 6(1), 38–51. doi:10.1038/nrc1779.
Bordonaro, M., Lazarova, D. L., & Sartorelli, A. C. (2007). The activation of beta-catenin by Wnt signaling mediates the effects of histone deacetylase inhibitors. Experimental Cell Research, 313(8), 1652–1666. doi:10.1016/j.yexcr.2007.02.008.
Federico, M., & Bagella, L. (2011). Histone deacetylase inhibitors in the treatment of hematological malignancies and solid tumors. Journal of Biomedicine and Biotechnology, 2011(Figure 1), 475641. doi:10.1155/2011/475641.
Dashwood, R. H., & Ho, E. (2007). Dietary histone deacetylase inhibitors: from cells to mice to man. Seminars in Cancer Biology, 17(5), 363–369. doi:10.1016/j.semcancer.2007.04.001.
Kuefer, R., Hofer, M. D., Altug, V., Zorn, C., Genze, F., Kunzi-Rapp, K., … & Gschwend, J. E. (2004). Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer. British Journal of Cancer, 90(2), 535–41. doi:10.1038/sj.bjc.6601510.
Wang, Z., Ehinger, M., & Grant, S. (1999). Induction of apoptosis in U937 human leukemia cells by suberoylanilide hydroxamic acid ( SAHA ) proceeds through pathways that are regulated by, 7016–7025.
Davie, J. R. (2003). Inhibition of histone deacetylase activity by butyrate. The Journal of nutrition, 2485–2493.
Roy, M.-J., Dionne, S., Marx, G., Qureshi, I., Sarma, D., Levy, E., & Seidman, E. G. (2009). In vitro studies on the inhibition of colon cancer by butyrate and carnitine. Nutrition (Burbank, Los Angeles County, California), 25(11-12), 1193–1201. doi:10.1016/j.nut.2009.04.008.
Yu, D. C. W., Waby, J. S., Chirakkal, H., Staton, C. A., & Corfe, B. M. (2010). Butyrate suppresses expression of neuropilin I in colorectal cell lines through inhibition of Sp1 transactivation. Molecular Cancer, 9(1), 276. doi:10.1186/1476-4598-9-276.
Hernandez, A., Thomas, R., Smith, F., Sandberg, J., Kim, S., Chung, D. H., & Evers, B. M. (2001). Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. Surgery, 130(2), 265–272. doi:10.1067/msy.2001.115897.
Kim, Y.-H., Park, J.-W., Lee, J.-Y., & Kwon, T. K. (2004). Sodium butyrate sensitizes TRAIL-mediated apoptosis by induction of transcription from the DR5 gene promoter through Sp1 sites in colon cancer cells. Carcinogenesis, 25(10), 1813–1820. doi:10.1093/carcin/bgh188.
Niles, R. M. (1989). Sodium butyrate suppresses the transforming activity activated N-ras oncogene in human colon carcinoma cells. Experimental Cell Research, 184, 16–27.
Velázquez, O. C., Lederer, H. M., & Rombeau, J. L. (1996). Butyrate and the colonocyte. Implications for neoplasia. Digestive Diseases and Sciences, 41(4), 727–39. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/8674394.
Heruth, D. P., Zirnstein, G. W., Bradley, J. F., & Rothbergs, G. (1993). Sodium butyrate causes an increase in the block to transcriptional elongation in the c-myc gene in SW837 rectal carcinoma cells. The Journal of Biological Chemistry, 268(25), 20466–20472.
Taylora, C. W., & Kimb, Y. S. (1992). Sensitivity of nuclear c-myc levels and induction to agents in human colon tumor cell lines. Cancer Letters, 62(2), 95–105.
Giles, R. H., Lolkema, M. P., Snijckers, C. M., Belderbos, M., van der Groep, P., Mans, D. a, … & Voest, E. E. (2006). Interplay between VHL/HIF1alpha and Wnt/beta-catenin pathways during colorectal tumorigenesis. Oncogene, 25(21), 3065–70. doi:10.1038/sj.onc.1209330.
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., … & Ohno, H. (2013). Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells. Nature, 504(7480), 446–50. doi:10.1038/nature12721.
Qian, D. Z., Kachhap, S. K., Collis, S. J., Verheul, H. M. W., Carducci, M. A., Atadja, P., & Pili, R. (2006). Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1 alpha. Cancer Research, 66(17), 8814–8821. doi:10.1158/0008-5472.CAN-05-4598.
Sancho, E., Batlle, E., & Clevers, H. (2004). Signaling pathways in intestinal development and cancer. Annual Review of Cell and Developmental Biology, 20, 695–723. doi:10.1146/annurev.cellbio.20.010403.092805.
Billin, A. N., Thirlwell, H., & Ayer, D. E. (2000). Beta-catenin-histone deacetylase interactions regulate the transition of LEF1 from a transcriptional repressor to an activator. Molecular and cellular biology, 20(18), 6882–90. Retrieved from http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=88764&tool=pmcentrez&rendertype=abstract.
Yamaguchi, M., Tonou-Fujimori, N., Komori, A., Maeda, R., Nojima, Y., Li, H., … & Masai, I. (2005). Histone deacetylase 1 regulates retinal neurogenesis in zebrafish by suppressing Wnt and Notch signaling pathways. Development (Cambridge, England), 132(13), 3027–43. doi:10.1242/dev.01881.
Luczyńska, E., & Anioł, J. (2013). Neoangiogenesis in prostate cancer. Contemporary Oncology (Poznan, Poland), 17(3), 229–233. doi:10.5114/wo.2013.35272.
Pellizzaro, C., & Coradini, D. (2002). Modulation of angiogenesis-related proteins synthesis by sodium butyrate in colon cancer cell line HT29 sodium butyrate (NaB), a short-chain fatty acid naturally arrest, differentiation and apoptosis in colon cancer cells. Carcinogenesis, 23(5), 735–740.
Bates, S. E., Currier, S. J., Alvarez, M., & Fojo, A. T. (1992). Modulation of P-glycoprotein phosphorylation and drug transport by sodium butyrate. Biochemistry, 31(28), 6366–72. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/1352990.
Gonçalves, P., Gregório, I., & Martel, F. (2011). The short-chain fatty acid butyrate is a substrate of breast cancer resistance protein. American Journal of Physiology. Cell Physiology, 301(5), C984–C994. doi:10.1152/ajpcell.00146.2011.
Casalta-Lopes, J. (2011). Efflux pumps modulation in colorectal adenocarcinoma cell lines: the role of nuclear medicine. Journal of Cancer Therapy, 02(03), 408–417. doi:10.4236/jct.2011.23056.
Kwaan, H. C. B., & McMahon, B. (2009). Coagulation in cancer. (P. David Green, MD & H. C. Kwaan, Eds.) (pp. 43–66). Springer New York. Retrieved from http://scholar.google.com/scholar?hl=en&btnG=Search&q=intitle:No+Title#0.
Gibson, P. R., Birchall, I., Rosella, O., Albert, V., Finch, C. F., Barkla, D. H., & Young, G. P. (1998). Urokinase and the intestinal mucosa: evidence for a role in epithelial cell turnover. Gut, 43, 656–663.
Mortensen, F. V., Jørgensen, B., Christiansen, H. M., Sloth-Nielsen, J., Wolff, B., & Hessov, I. (2000). Short-chain fatty acid enemas stimulate plasminogen activator inhibitor-1 after abdominal aortic graft surgery: a double-blinded, placebo-controlled study. Thrombosis Research, 98(5), 361–366.
Shukla, S., & Meeran, S. M. (2014). Epigenetics of cancer stem cells: pathways and therapeutics. Biochimica et Biophysica Acta (BBA), 1840(12), 3494–3502.
Kato, K., Kuhara, A., Yoneda, T., Inoue, T., Takao, T., Ohgami, T., … & Wake, N. (2011). Sodium butyrate inhibits the self-renewal capacity of endometrial tumor side-population cells by inducing a DNA damage response. Molecular Cancer Therapeutics, 10(8), 1430–9. doi:10.1158/1535-7163.MCT-10-1062.
Rodríguez-Salvador, J., Armas-Pineda, C., Perezpeña-Diazconti, F., Chico-Ponce de León, G., Sosa-Sáinz, P., Lezama, F., … & Arenas-Huertero, F. (2005). Effect of sodium butyrate on pro-matrix metalloproteinase-9 and -2 differential secretion in pediatric tumors and cell lines. Journal of Experimental & Clinical Cancer Research, 24(3), 463–474.
Oukopoulos, P. L., Ungall, B. A. M., Traw, R. C. S., & Hornton, J. R. T. (2003). Matrix metalloproteinase-2 and -9 involvement in canine tumors. Veterinary Pathology, 394, 382–394.
Oba, K., Konno, H., Tanaka, T., Baba, M., Kamiya, K., Ohta, M., … & Nakamura, S. (2002). Prevention of liver metastasis of human colon cancer by selective matrix metalloproteinase inhibitor MMI-166. Cancer Letters, 175, 45–51.
Zeng, H., & Briske-Anderson, M. (2005). Nutrition and cancer prolonged butyrate treatment inhibits the migration and invasion potential of HT1080 tumor cells. The Journal of Nutrition, 291–295.
Pouillart, P. R. (1998). Role of butyric acid and its derivatives in the treatment of colorectal cancer and hemoglobinopathies. Life Sciences, 63(20), 1739–1760.
Egorin, M. J., Yuan, Z. M., Sentz, D. L., Plaisance, K., & Eiseman, J. L. (1999). Plasma pharmacokinetics of butyrate after intravenous administration of sodium butyrate or oral administration of tributyrin or sodium butyrate to mice and rats. Cancer Chemotherapy and Pharmacology, 43(6), 445–53. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10321503.
Marc, D., & Sausville, A. (1998). I study of the in patients orally with administered solid butyrate. 4(March), 629–634.
Bras–Gonçalves, R. A., Pocard, M., Formento‡, J., Poirson–Bichat, F., de Pinieux, G., Pandrea§, I., … & Poupon, M. (2001). Synergistic efficacy of 3n-butyrate and 5-fluorouracil in human colorectal cancer xenografts via modulation of DNA synthesis. Gastroenterology, 120(4), 874–888. doi:10.1053/gast.2001.22440.
Wang, T., Cai, G., Qiu, Y., Fei, N., Zhang, M., Pang, X., … & Zhao, L. (2012). Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. The ISME Journal, 6(2), 320–9. doi:10.1038/ismej.2011.109.
Lin, X. B., Farhangfar, A., Valcheva, R., Sawyer, M. B., Dieleman, L., Schieber, A., … & Baracos, V. (2014). The role of intestinal microbiota in development of irinotecan toxicity and in toxicity reduction through dietary fibres in rats. PloS One, 9(1), e83644. doi:10.1371/journal.pone.0083644.
Acknowledgments
Ana Salomé Pires would like to thank the Portuguese Foundation for Science and Technology for the award of PhD scholarship (SFRH/BD/75300/2010).
Support: FCT, Portugal (Strategic Project PEst-C/SAU/UI3282/2013 and UID/NEU/04539/2013), COMPETE-FEDER.
Conflict of interest
The authors declare that they have nothing to disclose.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Encarnação, J.C., Abrantes, A.M., Pires, A.S. et al. Revisit dietary fiber on colorectal cancer: butyrate and its role on prevention and treatment. Cancer Metastasis Rev 34, 465–478 (2015). https://doi.org/10.1007/s10555-015-9578-9
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10555-015-9578-9
Keywords
- Colorectal cancer
- Butyrate
- Histone deacetylase inhibitors
- Cancer prevention
- Cancer therapy