Generic placeholder image

Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

The Role of Diet Related Short-Chain Fatty Acids in Colorectal Cancer Metabolism and Survival: Prevention and Therapeutic Implications

Author(s): Sara Daniela Gomes, Cláudia Suellen Oliveira, João Azevedo-Silva, Marta R. Casanova, Judite Barreto, Helena Pereira, Susana R. Chaves, Lígia R. Rodrigues, Margarida Casal, Manuela Côrte-Real, Fátima Baltazar and Ana Preto*

Volume 27, Issue 24, 2020

Page: [4087 - 4108] Pages: 22

DOI: 10.2174/0929867325666180530102050

Price: $65


Colorectal Cancer (CRC) is a major cause of cancer-related death worldwide. CRC increased risk has been associated with alterations in the intestinal microbiota, with decreased production of Short Chain Fatty Acids (SCFAs). SCFAs produced in the human colon are the major products of bacterial fermentation of undigested dietary fiber and starch. While colonocytes use the three major SCFAs, namely acetate, propionate and butyrate, as energy sources, transformed CRC cells primarily undergo aerobic glycolysis. Compared to normal colonocytes, CRC cells exhibit increased sensitivity to SCFAs, thus indicating they play an important role in cell homeostasis. Manipulation of SCFA levels in the intestine, through changes in microbiota, has therefore emerged as a potential preventive/therapeutic strategy for CRC. Interest in understanding SCFAs mechanism of action in CRC cells has increased in the last years. Several SCFA transporters like SMCT-1, MCT-1 and aquaporins have been identified as the main transmembrane transporters in intestinal cells. Recently, it was shown that acetate promotes plasma membrane re-localization of MCT-1 and triggers changes in the glucose metabolism. SCFAs induce apoptotic cell death in CRC cells, and further mechanisms have been discovered, including the involvement of lysosomal membrane permeabilization, associated with mitochondria dysfunction and degradation.

In this review, we will discuss the current knowledge on the transport of SCFAs by CRC cells and their effects on CRC metabolism and survival. The impact of increasing SCFA production by manipulation of colon microbiota on the prevention/therapy of CRC will also be addressed.

Keywords: Colorectal cancer, short chain fatty acids, microbiota, cell death mechanism, metabolism, cell death, membrane transport.

Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108.
[] [PMID: 25651787]
Keku, T.O.; Dulal, S.; Deveaux, A.; Jovov, B.; Han, X. The gastrointestinal microbiota and colorectal cancer. Am. J. Physiol. Gastrointest. Liver Physiol., 2015, 308(5), G351-G363.
[] [PMID: 25540232]
Carr, P.R.; Jansen, L.; Bienert, S.; Roth, W.; Herpel, E.; Kloor, M.; Bläker, H.; Chang-Claude, J.; Brenner, H.; Hoffmeister, M. Associations of red and processed meat intake with major molecular pathological features of colorectal cancer. Eur. J. Epidemiol., 2017, 32(5), 409-418.
[] [PMID: 28646407]
Gao, Z.; Guo, B.; Gao, R.; Zhu, Q.; Qin, H. Microbiota disbiosis is associated with colorectal cancer. Front. Microbiol., 2015, 6, 20.
[] [PMID: 25699023]
Sobhani, I.; Amiot, A.; Le Baleur, Y.; Levy, M.; Auriault, M.L.; Van Nhieu, J.T.; Delchier, J.C. Microbial dysbiosis and colon carcinogenesis: could colon cancer be considered a bacteria-related disease? Therap. Adv. Gastroenterol., 2013, 6(3), 215-229.
[] [PMID: 23634186]
Sobhani, I.; Tap, J.; Roudot-Thoraval, F.; Roperch, J.P.; Letulle, S.; Langella, P.; Corthier, G.; Tran Van Nhieu, J.; Furet, J.P. Microbial dysbiosis in colorectal cancer (CRC) patients. PLoS One, 2011, 6(1)e16393
[] [PMID: 21297998]
Hamada, T.; Keum, N.; Nishihara, R.; Ogino, S. Molecular pathological epidemiology: new developing frontiers of big data science to study etiologies and pathogenesis. J. Gastroenterol., 2017, 52(3), 265-275.
[] [PMID: 27738762]
Hughes, L.A.E.; Simons, C.C.J.M.; van den Brandt, P.A.; van Engeland, M.; Weijenberg, M.P. Lifestyle, diet and colorectal cancer risk according to (EPI)genetic instability: current evidence and future directions of molecular pathological epidemiology. Curr. Colorectal Cancer Rep., 2017, 13(6), 455-469.
[] [PMID: 29249914]
Ogino, S.; Chan, A.T.; Fuchs, C.S.; Giovannucci, E. Molecular pathological epidemiology of colorectal neoplasia: an emerging transdisciplinary and interdisciplinary field. Gut, 2011, 60(3), 397-411.
[] [PMID: 21036793]
Gilsing, A.M.; Fransen, F.; de Kok, T.M.; Goldbohm, A.R.; Schouten, L.J.; de Bruïne, A.P.; van Engeland, M.; van den Brandt, P.A.; de Goeij, A.F.; Weijenberg, M.P. Dietary heme iron and the risk of colorectal cancer with specific mutations in KRAS and APC. Carcinogenesis, 2013, 34(12), 2757-2766.
[] [PMID: 23983135]
Li, W.; Qiu, T.; Ling, Y.; Guo, L.; Li, L.; Ying, J. Molecular pathological epidemiology of colorectal cancer in Chinese patients with KRAS and BRAF mutations. Oncotarget, 2015, 6(37), 39607-39613.
[] [PMID: 26530529]
Ogino, S.; Nowak, J.A.; Hamada, T.; Phipps, A.I.; Peters, U.; Milner, D.A., Jr; Giovannucci, E.L.; Nishihara, R.; Giannakis, M.; Garrett, W.S.; Song, M. Integrative analysis of exogenous, endogenous, tumour and immune factors for precision medicine. Gut, 2018, 67(6), 1168-1180.
[] [PMID: 29437869]
Inamura, K. Colorectal cancers: an update on their molecular pathology. Cancers (Basel), 2018, 10(1)E26
[] [PMID: 29361689]
Zeng, H.; Lazarova, D.L.; Bordonaro, M. Mechanisms linking dietary fiber, gut microbiota and colon cancer prevention. World J. Gastrointest. Oncol., 2014, 6(2), 41-51.
[] [PMID: 24567795]
Cipe, G.; Idiz, U.O.; Firat, D.; Bektasoglu, H. Relationship between intestinal microbiota and colorectal cancer. World J. Gastrointest. Oncol., 2015, 7(10), 233-240.
[] [PMID: 26483877]
Neish, A.S. Microbes in gastrointestinal health and disease. Gastroenterology, 2009, 136(1), 65-80.
[] [PMID: 19026645]
Liu, Z.; Cao, A.T.; Cong, Y. Microbiota regulation of inflammatory bowel disease and colorectal cancer. Semin. Cancer Biol., 2013, 23(6 Pt B), 543-552.
[] [PMID: 24071482]
Tiihonen, K.; Ouwehand, A.C.; Rautonen, N. Human intestinal microbiota and healthy ageing. Ageing Res. Rev., 2010, 9(2), 107-116.
[] [PMID: 19874918]
Holmes, E.; Li, J.V.; Athanasiou, T.; Ashrafian, H.; Nicholson, J.K. Understanding the role of gut microbiome-host metabolic signal disruption in health and disease. Trends Microbiol., 2011, 19(7), 349-359.
[] [PMID: 21684749]
Russell, W.R.; Hoyles, L.; Flint, H.J.; Dumas, M.E. Colonic bacterial metabolites and human health. Curr. Opin. Microbiol., 2013, 16(3), 246-254.
[] [PMID: 23880135]
Adom, D.; Nie, D. Regulation of autophagy by short chain fatty acids in colon cancer cells. Autophagy - A Double-Edged Sword - Cell Survival or Death? Intech., 2013, 522
Layden, B.T.; Angueira, A.R.; Brodsky, M.; Durai, V.; Lowe, W.L., Jr Short chain fatty acids and their receptors: new metabolic targets. Transl. Res., 2013, 161(3), 131-140.
[] [PMID: 23146568]
Kim, C.H.; Park, J.; Kim, M. Gut microbiota-derived short-chain Fatty acids, T cells, and inflammation. Immune Netw., 2014, 14(6), 277-288.
[] [PMID: 25550694]
Hosseini, E.; Grootaert, C.; Verstraete, W.; Van de Wiele, T. Propionate as a health-promoting microbial metabolite in the human gut. Nutr. Rev., 2011, 69(5), 245-258.
[] [PMID: 21521227]
Zhu, Y.; Michelle Luo, T.; Jobin, C.; Young, H.A. Gut microbiota and probiotics in colon tumorigenesis. Cancer Lett., 2011, 309(2), 119-127.
[] [PMID: 21741763]
Di Mauro, A.; Neu, J.; Riezzo, G.; Raimondi, F.; Martinelli, D.; Francavilla, R.; Indrio, F. Gastrointestinal function development and microbiota. Ital. J. Pediatr., 2013, 39, 15.
[] [PMID: 23433508]
Chen, W.; Liu, F.; Ling, Z.; Tong, X.; Xiang, C. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One, 2012, 7(6)e39743
[] [PMID: 22761885]
Neish, A.S. Mucosal immunity and the microbiome. Ann. Am. Thorac. Soc., 2014, 11(Suppl. 1), S28-S32.
[] [PMID: 24437401]
Keku, T.O.; Dulal, S.; Deveaux, A.; Jovov, B.; Han, X. The gastrointestinal microbiota and colorectal cancer. Am. J. Physiol. Gastrointest. Liver Physiol., 2015, 308(5), G351-G363.
[] [PMID: 25540232]
Leung, A.; Tsoi, H.; Yu, J. Fusobacterium and Escherichia: models of colorectal cancer driven by microbiota and the utility of microbiota in colorectal cancer screening. Expert Rev. Gastroenterol. Hepatol., 2015, 9(5), 651-657.
[] [PMID: 25582922]
Yang, Y.; Jobin, C. Microbial imbalance and intestinal pathologies: connections and contributions. Dis. Model. Mech., 2014, 7(10), 1131-1142.
[] [PMID: 25256712]
Kostic, A.D.; Chun, E.; Robertson, L.; Glickman, J.N.; Gallini, C.A.; Michaud, M.; Clancy, T.E.; Chung, D.C.; Lochhead, P.; Hold, G.L.; El-Omar, E.M.; Brenner, D.; Fuchs, C.S.; Meyerson, M.; Garrett, W.S. Fusobacterium nucleatum potentiates intestinal tumorigenesis and modulates the tumor-immune microenvironment. Cell Host Microbe, 2013, 14(2), 207-215.
[] [PMID: 23954159]
Nistal, E.; Fernández-Fernández, N.; Vivas, S.; Olcoz, J.L. Factors determining colorectal cancer: the role of the intestinal microbiota. Front. Oncol., 2015, 5, 220.
[] [PMID: 26528432]
Kostic, A.D.; Gevers, D.; Pedamallu, C.S.; Michaud, M.; Duke, F.; Earl, A.M.; Ojesina, A.I.; Jung, J.; Bass, A.J.; Tabernero, J.; Baselga, J.; Liu, C.; Shivdasani, R.A.; Ogino, S.; Birren, B.W.; Huttenhower, C.; Garrett, W.S.; Meyerson, M. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res., 2012, 22(2), 292-298.
[] [PMID: 22009990]
Castellarin, M.; Warren, R.L.; Freeman, J.D.; Dreolini, L.; Krzywinski, M.; Strauss, J.; Barnes, R.; Watson, P.; Allen-Vercoe, E.; Moore, R.A.; Holt, R.A. Fusobacterium nucleatum infection is prevalent in human colorectal carcinoma. Genome Res., 2012, 22(2), 299-306.
[] [PMID: 22009989]
Tahara, T.; Yamamoto, E.; Suzuki, H.; Maruyama, R.; Chung, W.; Garriga, J.; Jelinek, J.; Yamano, H.O.; Sugai, T.; An, B.; Shureiqi, I.; Toyota, M.; Kondo, Y.; Estécio, M.R.; Issa, J.P. Fusobacterium in colonic flora and molecular features of colorectal carcinoma. Cancer Res., 2014, 74(5), 1311-1318.
[] [PMID: 24385213]
Nosho, K.; Sukawa, Y.; Adachi, Y.; Ito, M.; Mitsuhashi, K.; Kurihara, H.; Kanno, S.; Yamamoto, I.; Ishigami, K.; Igarashi, H.; Maruyama, R.; Imai, K.; Yamamoto, H.; Shinomura, Y. Association of Fusobacterium nucleatum with immunity and molecular alterations in colorectal cancer. World J. Gastroenterol., 2016, 22(2), 557-566.
[] [PMID: 26811607]
Mehta, R.S.; Nishihara, R.; Cao, Y.; Song, M.; Mima, K.; Qian, Z.R.; Nowak, J.A.; Kosumi, K.; Hamada, T.; Masugi, Y.; Bullman, S.; Drew, D.A.; Kostic, A.D.; Fung, T.T.; Garrett, W.S.; Huttenhower, C.; Wu, K.; Meyerhardt, J.A.; Zhang, X.; Willett, W.C.; Giovannucci, E.L.; Fuchs, C.S.; Chan, A.T.; Ogino, S. Association of dietary patterns with risk of colorectal cancer subtypes classified by fusobacterium nucleatum in tumor tissue. JAMA Oncol., 2017, 3(7), 921-927.
[] [PMID: 28125762]
Mima, K.; Nishihara, R.; Qian, Z.R.; Cao, Y.; Sukawa, Y.; Nowak, J.A.; Yang, J.; Dou, R.; Masugi, Y.; Song, M.; Kostic, A.D.; Giannakis, M.; Bullman, S.; Milner, D.A.; Baba, H.; Giovannucci, E.L.; Garraway, L.A.; Freeman, G.J.; Dranoff, G.; Garrett, W.S.; Huttenhower, C.; Meyerson, M.; Meyerhardt, J.A.; Chan, A.T.; Fuchs, C.S.; Ogino, S. Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis. Gut, 2016, 65(12), 1973-1980.
[] [PMID: 26311717]
Yang, Y.; Weng, W.; Peng, J.; Hong, L.; Yang, L.; Toiyama, Y.; Gao, R.; Liu, M.; Yin, M.; Pan, C.; Li, H.; Guo, B.; Zhu, Q.; Wei, Q.; Moyer, M.P.; Wang, P.; Cai, S.; Goel, A.; Qin, H.; Ma, Y. Fusobacterium nucleatum increases proliferation of colorectal cancer cells and tumor development in mice by activating toll-like receptor 4 signaling to nuclear factorkappa b, and up-regulating expression of microRNA-21., 2017, 152(4), 851-866.
[] [PMID: 27876571]
Ye, X.; Wang, R.; Bhattacharya, R.; Boulbes, D.R.; Fan, F.; Xia, L.; Adoni, H.; Ajami, N.J.; Wong, M.C.; Smith, D.P.; Petrosino, J.F.; Venable, S.; Qiao, W.; Baladandayuthapani, V.; Maru, D.; Ellis, L.M. Fusobacterium nucleatum subspecies animalis influences proinflammatory cytokine expression and monocyte activation in human colorectal tumors. Cancer Prev. Res. (Phila.), 2017, 10(7), 398-409.
[] [PMID: 28483840]
Ohigashi, S.; Sudo, K.; Kobayashi, D.; Takahashi, O.; Takahashi, T.; Asahara, T.; Nomoto, K.; Onodera, H. Changes of the intestinal microbiota, short chain fatty acids, and fecal pH in patients with colorectal cancer. Dig. Dis. Sci., 2013, 58(6), 1717-1726.
[] [PMID: 23306850]
Nedjadi, T.; Moran, A.W.; Al-Rammahi, M.A.; Shirazi-Beechey, S.P. Characterization of butyrate transport across the luminal membranes of equine large intestine. Exp. Physiol., 2014, 99(10), 1335-1347.
[] [PMID: 25172888]
Mortensen, P.B.; Clausen, M.R. Short-chain fatty acids in the human colon: relation to gastrointestinal health and disease. Scand. J. Gastroenterol. Suppl., 1996, 216, 132-148.
[] [PMID: 8726286]
Macfarlane, G.T.; Macfarlane, S. Bacteria, colonic fermentation, and gastrointestinal health. J. AOAC Int., 2012, 95(1), 50-60.
[] [PMID: 22468341]
Alles, M.S.; Hartemink, R.; Meyboom, S.; Harryvan, J.L.; Van Laere, K.M.; Nagengast, F.M.; Hautvast, J.G. Effect of transgalactooligosaccharides on the composition of the human intestinal microflora and on putative risk markers for colon cancer. Am. J. Clin. Nutr., 1999, 69(5), 980-991.
[] [PMID: 10232640]
Jenkins, D.J.; Kendall, C.W.; Vuksan, V.; Augustin, L.S.; Li, Y.M.; Lee, B.; Mehling, C.C.; Parker, T.; Faulkner, D.; Seyler, H.; Vidgen, E.; Fulgoni, V. The effect of wheat bran particle size on laxation and colonic fermentation. J. Am. Coll. Nutr., 1999, 18(4), 339-345.
[] [PMID: 12038477]
Topping, D.L.; Clifton, P.M. Short-chain fatty acids and human colonic function: roles of resistant starch and nonstarch polysaccharides. Physiol. Rev., 2001, 81(3), 1031-1064.
[] [PMID: 11427691]
Scheppach, W.; Bartram, H.P.; Richter, F. Role of short-chain fatty acids in the prevention of colorectal cancer. Eur. J. Cancer, 1995, 31A(7-8), 1077-1080.
[] [PMID: 7576995]
Canani, R.B.; Costanzo, M.D.; Leone, L.; Pedata, M.; Meli, R.; Calignano, A. Potential beneficial effects of butyrate in intestinal and extraintestinal diseases. World J. Gastroenterol., 2011, 17(12), 1519-1528.
[] [PMID: 21472114]
Du, X.; Shi, H.; Li, J.; Dong, Y.; Liang, J.; Ye, J.; Kong, S.; Zhang, S.; Zhong, T.; Yuan, Z.; Xu, T.; Zhuang, Y.; Zheng, B.; Geng, J.G.; Tao, W. Mst1/Mst2 regulate development and function of regulatory T cells through modulation of Foxo1/Foxo3 stability in autoimmune disease. J. Immunol., 2014, 192(4), 1525-1535.
[] [PMID: 24453252]
Cummings, J.H.; Pomare, E.W.; Branch, W.J.; Naylor, C.P.; Macfarlane, G.T. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut, 1987, 28(10), 1221-1227.
[] [PMID: 3678950]
Boets, E.; Deroover, L.; Houben, E.; Vermeulen, K.; Gomand, S.V.; Delcour, J.A.; Verbeke, K. Quantification of in vivo colonic short chain fatty acid production from inulin. Nutrients, 2015, 7(11), 8916-8929.
[] [PMID: 26516911]
Hijova, E.; Chmelarova, A. Short chain fatty acids and colonic health. Bratisl. Lek Listy, 2007, 108(8), 354-358.
[PMID: 18203540]
Ganapathy, V.; Thangaraju, M.; Prasad, P.D.; Martin, P.M.; Singh, N. Transporters and receptors for short-chain fatty acids as the molecular link between colonic bacteria and the host. Curr. Opin. Pharmacol., 2013, 13(6), 869-874.
[] [PMID: 23978504]
Gonçalves, P.; Martel, F. Butyrate and colorectal cancer: the role of butyrate transport. Curr. Drug Metab., 2013, 14(9), 994-1008.
[] [PMID: 24160296]
Hadjiagapiou, C.; Schmidt, L.; Dudeja, P.K.; Layden, T.J.; Ramaswamy, K. Mechanism(s) of butyrate transport in Caco-2 cells: role of monocarboxylate transporter 1. Am. J. Physiol. Gastrointest. Liver Physiol., 2000, 279(4), G775-G780.
[] [PMID: 11005765]
Moschen, I.; Bröer, A.; Galić, S.; Lang, F.; Bröer, S. Significance of short chain fatty acid transport by members of the monocarboxylate transporter family (MCT). Neurochem. Res., 2012, 37(11), 2562-2568.
[] [PMID: 22878645]
Halestrap, A.P. The SLC16 gene family - structure, role and regulation in health and disease. Mol. Aspects Med., 2013, 34(2-3), 337-349.
[] [PMID: 23506875]
Pinheiro, C.; Longatto-Filho, A.; Azevedo-Silva, J.; Casal, M.; Schmitt, F.C.; Baltazar, F. Role of monocarboxylate transporters in human cancers: state of the art. J. Bioenerg. Biomembr., 2012, 44(1), 127-139.
[] [PMID: 22407107]
Halestrap, A.P.; Meredith, D. The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond. Pflugers Arch., 2004, 447(5), 619-628.
[] [PMID: 12739169]
Baltazar, F.; Pinheiro, C.; Morais-Santos, F.; Azevedo-Silva, J.; Queirós, O.; Preto, A.; Casal, M. Monocarboxylate transporters as targets and mediators in cancer therapy response. Histol. Histopathol., 2014, 29(12), 1511-1524.
[PMID: 24921258]
Pinheiro, C.; Longatto-Filho, A.; Scapulatempo, C.; Ferreira, L.; Martins, S.; Pellerin, L.; Rodrigues, M.; Alves, V.A.; Schmitt, F.; Baltazar, F. Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas. Virchows Arch., 2008, 452(2), 139-146.
[] [PMID: 18188595]
Froberg, M.K.; Gerhart, D.Z.; Enerson, B.E.; Manivel, C.; Guzman-Paz, M.; Seacotte, N.; Drewes, L.R. Expression of monocarboxylate transporter MCT1 in normal and neoplastic human CNS tissues. Neuroreport, 2001, 12(4), 761-765.
[] [PMID: 11277580]
Pinheiro, C.; Albergaria, A.; Paredes, J.; Sousa, B.; Dufloth, R.; Vieira, D.; Schmitt, F.; Baltazar, F. Monocarboxylate transporter 1 is up-regulated in basal-like breast carcinoma. Histopathology, 2010, 56(7), 860-867.
[] [PMID: 20636790]
Ladanyi, M.; Antonescu, C.R.; Drobnjak, M.; Baren, A.; Lui, M.Y.; Golde, D.W.; Cordon-Cardo, C. The precrystalline cytoplasmic granules of alveolar soft part sarcoma contain monocarboxylate transporter 1 and CD147. Am. J. Pathol., 2002, 160(4), 1215-1221.
[] [PMID: 11943706]
Chen, H.; Wang, L.; Beretov, J.; Hao, J.; Xiao, W.; Li, Y. Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression. Clin. Exp. Metastasis, 2010, 27(8), 557-569.
[] [PMID: 20658178]
Pértega-Gomes, N.; Vizcaíno, J.R.; Miranda-Gonçalves, V.; Pinheiro, C.; Silva, J.; Pereira, H.; Monteiro, P.; Henrique, R.M.; Reis, R.M.; Lopes, C.; Baltazar, F. Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer. BMC Cancer, 2011, 11(312), 1-9.
[] [PMID: 21787388]
Pinheiro, C.; Longatto-Filho, A.; Simões, K.; Jacob, C.E.; Bresciani, C.J.; Zilberstein, B.; Cecconello, I.; Alves, V.A.; Schmitt, F.; Baltazar, F. The prognostic value of CD147/EMMPRIN is associated with monocarboxylate transporter 1 co-expression in gastric cancer. Eur. J. Cancer, 2009, 45(13), 2418-2424.
[] [PMID: 19628385]
Romero-Garcia, S.; Moreno-Altamirano, M.M.; Prado-Garcia, H.; Sánchez-García, F.J. Lactate contribution to the tumor microenvironment: mechanisms, effects on immune cells and therapeutic relevance. Front. Immunol., 2016, 7, 52.
[] [PMID: 26909082]
Kirat, D.; Masuoka, J.; Hayashi, H.; Iwano, H.; Yokota, H.; Taniyama, H.; Kato, S. Monocarboxylate transporter 1 (MCT1) plays a direct role in short-chain fatty acids absorption in caprine rumen. J. Physiol., 2006, 576(Pt 2), 635-647.
[] [PMID: 16901943]
Kirat, D.; Kato, S. Monocarboxylate transporter 1 (MCT1) mediates transport of short-chain fatty acids in bovine caecum. Exp. Physiol., 2006, 91(5), 835-844.
[] [PMID: 16857719]
den Besten, G.; Lange, K.; Havinga, R.; van Dijk, T.H.; Gerding, A.; van Eunen, K.; Müller, M.; Groen, A.K.; Hooiveld, G.J.; Bakker, B.M.; Reijngoud, D.J. Gut-derived short-chain fatty acids are vividly assimilated into host carbohydrates and lipids. Am. J. Physiol. Gastrointest. Liver Physiol., 2013, 305(12), G900-G910.
[] [PMID: 24136789]
Fung, K.Y.; Cosgrove, L.; Lockett, T.; Head, R.; Topping, D.L. A review of the potential mechanisms for the lowering of colorectal oncogenesis by butyrate. Br. J. Nutr., 2012, 108(5), 820-831.
[] [PMID: 22676885]
Thangaraju, M.; Cresci, G.; Itagaki, S.; Mellinger, J.; Browning, D.D.; Berger, F.G.; Prasad, P.D.; Ganapathy, V. Sodium-coupled transport of the short chain fatty acid butyrate by SLC5A8 and its relevance to colon cancer. J. Gastrointest. Surg., 2008, 12(10), 1773-1781.
[] [PMID: 18661192]
Babu, E.; Ramachandran, S.; CoothanKandaswamy, V.; Elangovan, S.; Prasad, P.D.; Ganapathy, V.; Thangaraju, M. Role of SLC5A8, a plasma membrane transporter and a tumor suppressor, in the antitumor activity of dichloroacetate. Oncogene, 2011, 30(38), 4026-4037.
[] [PMID: 21499304]
Li, H.; Myeroff, L.; Smiraglia, D.; Romero, M.F.; Pretlow, T.P.; Kasturi, L.; Lutterbaugh, J.; Rerko, R.M.; Casey, G.; Issa, J.P.; Willis, J.; Willson, J.K.; Plass, C.; Markowitz, S.D. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc. Natl. Acad. Sci. USA, 2003, 100(14), 8412-8417.
[] [PMID: 12829793]
Ferro, S.; Azevedo-Silva, J.; Casal, M.; Côrte-Real, M.; Baltazar, F.; Preto, A. Characterization of acetate transport in colorectal cancer cells and potential therapeutic implications. Oncotarget, 2016, 7(43), 70639-70653.
[] [PMID: 28874966]
Kim, M.H. Short-chain fatty acids activate GPR41 and GPR43 on intestinal epithelial cells to promote inflammatory responses in mice Gastroenterology, 2013, 145(2), 396-406.
Kuwahara, A. Contributions of colonic short-chain Fatty Acid receptors in energy homeostasis. Front. Endocrinol. (Lausanne), 2014, 5, 144.
[] [PMID: 25228897]
Kasubuchi, M.; Hasegawa, S.; Hiramatsu, T.; Ichimura, A.; Kimura, I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients, 2015, 7(4), 2839-2849.
[] [PMID: 25875123]
Ahmad, M.S.; Krishnan, S.; Ramakrishna, B.S.; Mathan, M.; Pulimood, A.B.; Murthy, S.N. Butyrate and glucose metabolism by colonocytes in experimental colitis in mice. Gut, 2000, 46(4), 493-499.
[] [PMID: 10716678]
Donohoe, D.R.; Collins, L.B.; Wali, A.; Bigler, R.; Sun, W.; Bultman, S.J. The Warburg effect dictates the mechanism of butyrate-mediated histone acetylation and cell proliferation. Mol. Cell, 2012, 48(4), 612-626.
[] [PMID: 23063526]
Comalada, M.; Bailón, E.; de Haro, O.; Lara-Villoslada, F.; Xaus, J.; Zarzuelo, A.; Gálvez, J. The effects of short-chain fatty acids on colon epithelial proliferation and survival depend on the cellular phenotype. J. Cancer Res. Clin. Oncol., 2006, 132(8), 487-497.
[] [PMID: 16788843]
Scott, K.P.; Gratz, S.W.; Sheridan, P.O.; Flint, H.J.; Duncan, S.H. The influence of diet on the gut microbiota. Pharmacol. Res., 2013, 69(1), 52-60.
[] [PMID: 23147033]
Tang, Y.; Chen, Y.; Jiang, H.; Nie, D. The role of short-chain fatty acids in orchestrating two types of programmed cell death in colon cancer. Autophagy, 2011, 7(2), 235-237.
[] [PMID: 21160278]
Sakata, T. Stimulatory effect of short-chain fatty acids on epithelial cell proliferation in the rat intestine: a possible explanation for trophic effects of fermentable fibre, gut microbes and luminal trophic factors. Br. J. Nutr., 1987, 58(1), 95-103.
[] [PMID: 3620440]
Sauer, J.; Richter, K.K.; Pool-Zobel, B.L. Products formed during fermentation of the prebiotic inulin with human gut flora enhance expression of biotransformation genes in human primary colon cells. Br. J. Nutr., 2007, 97(5), 928-937.
[] [PMID: 17381985]
Imbernon, M.; Whyte, L.; Diaz-Arteaga, A.; Russell, W.R.; Moreno, N.R.; Vazquez, M.J.; Gonzalez, C.R.; Díaz-Ruiz, A.; Lopez, M.; Malagón, M.M.; Ross, R.A.; Dieguez, C.; Nogueiras, R. Regulation of GPR55 in rat white adipose tissue and serum LPI by nutritional status, gestation, gender and pituitary factors. Mol. Cell. Endocrinol., 2014, 383(1-2), 159-169.
[] [PMID: 24378736]
Zhang, Y.; Zhou, L.; Bao, Y.L.; Wu, Y.; Yu, C.L.; Huang, Y.X.; Sun, Y.; Zheng, L.H.; Li, Y.X. Butyrate induces cell apoptosis through activation of JNK MAP kinase pathway in human colon cancer RKO cells. Chem. Biol. Interact., 2010, 185(3), 174-181.
[] [PMID: 20346929]
Sengupta, S.; Muir, J.G.; Gibson, P.R. Does butyrate protect from colorectal cancer? J. Gastroenterol. Hepatol., 2006, 21(1 Pt 2), 209-218.
[] [PMID: 16460475]
Matthews, G.M.; Howarth, G.S.; Butler, R.N. Short-chain fatty acids induce apoptosis in colon cancer cells associated with changes to intracellular redox state and glucose metabolism. Chemotherapy, 2012, 58(2), 102-109.
[] [PMID: 22488147]
Scharlau, D.; Borowicki, A.; Habermann, N.; Hofmann, T.; Klenow, S.; Miene, C.; Munjal, U.; Stein, K.; Glei, M. Mechanisms of primary cancer prevention by butyrate and other products formed during gut flora-mediated fermentation of dietary fibre. Mutat. Res., 2009, 682(1), 39-53.
[] [PMID: 19383551]
Kiefer, J.; Beyer-Sehlmeyer, G.; Pool-Zobel, B.L. Mixtures of SCFA, composed according to physiologically available concentrations in the gut lumen, modulate histone acetylation in human HT29 colon cancer cells. Br. J. Nutr., 2006, 96(5), 803-810.
[] [PMID: 17092367]
Hinnebusch, B.F.; Meng, S.; Wu, J.T.; Archer, S.Y.; Hodin, R.A. The effects of short-chain fatty acids on human colon cancer cell phenotype are associated with histone hyperacetylation. J. Nutr., 2002, 132(5), 1012-1017.
[] [PMID: 11983830]
Mariadason, J.M.; Velcich, A.; Wilson, A.J.; Augenlicht, L.H.; Gibson, P.R. Resistance to butyrate-induced cell differentiation and apoptosis during spontaneous Caco-2 cell differentiation. Gastroenterology, 2001, 120(4), 889-899.
[] [PMID: 11231943]
Archer, S.Y.; Meng, S.; Shei, A.; Hodin, R.A. p21(WAF1) is required for butyrate-mediated growth inhibition of human colon cancer cells. Proc. Natl. Acad. Sci. USA, 1998, 95(12), 6791-6796.
[] [PMID: 9618491]
Davido, D.J.; Richter, F.; Boxberger, F.; Stahl, A.; Menzel, T.; Lührs, H.; Löffler, S.; Dusel, G.; Rapp, U.R.; Scheppach, W. Butyrate and propionate downregulate ERK phosphorylation in HT-29 colon carcinoma cells prior to differentiation. Eur. J. Cancer Prev., 2001, 10(4), 313-321.
[] [PMID: 11535873]
Gonçalves, P.; Araújo, J.R.; Pinho, M.J.; Martel, F. In vitro studies on the inhibition of colon cancer by butyrate and polyphenolic compounds. Nutr. Cancer, 2011, 63(2), 282-294.
[] [PMID: 21207318]
He, L.; Li, X.; Luo, H.S.; Rong, H.; Cai, J. Possible mechanism for the regulation of glucose on proliferation, inhibition and apoptosis of colon cancer cells induced by sodium butyrate. World J. Gastroenterol., 2007, 13(29), 4015-4018.
[] [PMID: 17663521]
Wong, J.M.; de Souza, R.; Kendall, C.W.; Emam, A.; Jenkins, D.J. Colonic health: fermentation and short chain fatty acids. J. Clin. Gastroenterol., 2006, 40(3), 235-243.
[] [PMID: 16633129]
Shao, Y.; Gao, Z.; Marks, P.A.; Jiang, X. Apoptotic and autophagic cell death induced by histone deacetylase inhibitors. Proc. Natl. Acad. Sci. USA, 2004, 101(52), 18030-18035.
[] [PMID: 15596714]
Li, R.W.; Li, C. Butyrate induces profound changes in gene expression related to multiple signal pathways in bovine kidney epithelial cells. BMC Genomics, 2006, 7, 234.
[] [PMID: 16972989]
Barshishat, M.; Polak-Charcon, S.; Schwartz, B. Butyrate regulates E-cadherin transcription, isoform expression and intracellular position in colon cancer cells. Br. J. Cancer, 2000, 82(1), 195-203.
[] [PMID: 10638989]
Chen, W.; Liu, F.; Ling, Z.; Tong, X.; Xiang, C. Human intestinal lumen and mucosa-associated microbiota in patients with colorectal cancer. PLoS One, 2012, 7(6)e39743
[] [PMID: 22761885]
Sambucetti, L.C.; Fischer, D.D.; Zabludoff, S.; Kwon, P.O.; Chamberlin, H.; Trogani, N.; Xu, H.; Cohen, D. Histone deacetylase inhibition selectively alters the activity and expression of cell cycle proteins leading to specific chromatin acetylation and antiproliferative effects. J. Biol. Chem., 1999, 274(49), 34940-34947.
[] [PMID: 10574969]
Iacomino, G.; Tecce, M.F.; Grimaldi, C.; Tosto, M.; Russo, G.L. Transcriptional response of a human colon adenocarcinoma cell line to sodium butyrate. Biochem. Biophys. Res. Commun., 2001, 285(5), 1280-1289.
[] [PMID: 11478796]
Marchion, D.; Münster, P. Development of histone deacetylase inhibitors for cancer treatment. Expert Rev. Anticancer Ther., 2007, 7(4), 583-598.
[] [PMID: 17428177]
Gonçalves, P.; Martel, F. Regulation of colonic epithelial butyrate transport: Focus on colorectal cancer. Porto Biomed J, 2016, 1(3), 83-91.
[] [PMID: 32258556]
Gonçalves, P. Modulation of butyrate transport in Caco-2 cells, 2008. Vol. 379, pp. 325-336,
Jan, G.; Belzacq, A.S.; Haouzi, D.; Rouault, A.; Métivier, D.; Kroemer, G.; Brenner, C. Propionibacteria induce apoptosis of colorectal carcinoma cells via short-chain fatty acids acting on mitochondria. Cell Death Differ., 2002, 9(2), 179-188.
[] [PMID: 11840168]
Tang, Y.; Chen, Y.; Jiang, H.; Nie, D. Short-chain fatty acids induced autophagy serves as an adaptive strategy for retarding mitochondria-mediated apoptotic cell death. Cell Death Differ., 2011, 18(4), 602-618.
[] [PMID: 20930850]
Kiefer, J.; Beyer-Sehlmeyer, G.; Pool-Zobel, B.L. Mixtures of SCFA, composed according to physiologically available concentrations in the gut lumen, modulate histone acetylation in human HT29 colon cancer cells. Br. J. Nutr., 2006, 96(5), 803-810.
[] [PMID: 17092367]
Lan, A.; Lagadic-Gossmann, D.; Lemaire, C.; Brenner, C.; Jan, G. Acidic extracellular pH shifts colorectal cancer cell death from apoptosis to necrosis upon exposure to propionate and acetate, major end-products of the human probiotic propionibacteria. Apoptosis, 2007, 12(3), 573-591.
[] [PMID: 17195096]
Tedelind, S.; Westberg, F.; Kjerrulf, M.; Vidal, A. Anti-inflammatory properties of the short-chain fatty acids acetate and propionate: a study with relevance to inflammatory bowel disease. World J. Gastroenterol., 2007, 13(20), 2826-2832.
[] [PMID: 17569118]
Pereira, C.; Silva, R.D.; Saraiva, L.; Johansson, B.; Sousa, M.J.; Côrte-Real, M. Mitochondria-dependent apoptosis in yeast. Biochim. Biophys. Acta, 2008, 1783(7), 1286-1302.
[] [PMID: 18406358]
Guaragnella, N.; Zdralević, M.; Antonacci, L.; Passarella, S.; Marra, E.; Giannattasio, S. The role of mitochondria in yeast programmed cell death. Front. Oncol., 2012, 2, 70.
[] [PMID: 22783546]
Ludovico, P.; Rodrigues, F.; Almeida, A.; Silva, M.T.; Barrientos, A.; Côrte-Real, M. Cytochrome c release and mitochondria involvement in programmed cell death induced by acetic acid in Saccharomyces cerevisiae. Mol. Biol. Cell, 2002, 13(8), 2598-2606.
[] [PMID: 12181332]
Fannjiang, Y.; Cheng, W.C.; Lee, S.J.; Qi, B.; Pevsner, J.; McCaffery, J.M.; Hill, R.B.; Basañez, G.; Hardwick, J.M. Mitochondrial fission proteins regulate programmed cell death in yeast. Genes Dev., 2004, 18(22), 2785-2797.
[] [PMID: 15520274]
Wissing, S.; Ludovico, P.; Herker, E.; Büttner, S.; Engelhardt, S.M.; Decker, T.; Link, A.; Proksch, A.; Rodrigues, F.; Corte-Real, M.; Fröhlich, K.U.; Manns, J.; Candé, C.; Sigrist, S.J.; Kroemer, G.; Madeo, F. An AIF orthologue regulates apoptosis in yeast. J. Cell Biol., 2004, 166(7), 969-974.
[] [PMID: 15381687]
Büttner, S.; Eisenberg, T.; Carmona-Gutierrez, D.; Ruli, D.; Knauer, H.; Ruckenstuhl, C.; Sigrist, C.; Wissing, S.; Kollroser, M.; Fröhlich, K.U.; Sigrist, S.; Madeo, F. Endonuclease G regulates budding yeast life and death. Mol. Cell, 2007, 25(2), 233-246.
[] [PMID: 17244531]
Kroemer, G.; Galluzzi, L.; Brenner, C. Mitochondrial membrane permeabilization in cell death. Physiol. Rev., 2007, 87(1), 99-163.
[] [PMID: 17237344]
Pereira, C.; Camougrand, N.; Manon, S.; Sousa, M.J.; Côrte-Real, M. ADP/ATP carrier is required for mitochondrial outer membrane permeabilization and cytochrome c release in yeast apoptosis. Mol. Microbiol., 2007, 66(3), 571-582.
[] [PMID: 17822411]
Pereira, C.; Chaves, S.; Alves, S.; Salin, B.; Camougrand, N.; Manon, S.; Sousa, M.J.; Côrte-Real, M. Mitochondrial degradation in acetic acid-induced yeast apoptosis: the role of Pep4 and the ADP/ATP carrier. Mol. Microbiol., 2010, 76(6), 1398-1410.
[] [PMID: 20345665]
Pereira, H.; Azevedo, F.; Rego, A.; Sousa, M.J.; Chaves, S.R.; Côrte-Real, M. The protective role of yeast cathepsin D in acetic acid-induced apoptosis depends on ANT (Aac2p) but not on the voltage-dependent channel (Por1p). FEBS Lett., 2013, 587(2), 200-205.
[] [PMID: 23220089]
Oliveira, C.S.; Pereira, H.; Alves, S.; Castro, L.; Baltazar, F.; Chaves, S.R.; Preto, A.; Côrte-Real, M. Cathepsin D protects colorectal cancer cells from acetate-induced apoptosis through autophagy-independent degradation of damaged mitochondria. Cell Death Dis., 2015, 6e1788
[] [PMID: 26086961]
Marques, C.; Oliveira, C.S.; Alves, S.; Chaves, S.R.; Coutinho, O.P.; Côrte-Real, M.; Preto, A. Acetate-induced apoptosis in colorectal carcinoma cells involves lysosomal membrane permeabilization and cathepsin D release. Cell Death Dis., 2013, 4e507
[] [PMID: 23429293]
Liu, T.; Li, J.; Liu, Y.; Xiao, N.; Suo, H.; Xie, K.; Yang, C.; Wu, C. 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, 2012, 35(5), 1676-1684.
[] [PMID: 22669487]
Qu, W.; Yuan, X.; Zhao, J.; Zhang, Y.; Hu, J.; Wang, J.; Li, J. Dietary advanced glycation end products modify gut microbial composition and partially increase colon permeability in rats. Mol. Nutr. Food Res., 2017, 61(10)
[] [PMID: 28621836]
Del Pino-García, R.; Rivero-Pérez, M.D.; González-SanJosé, M.L.; Ortega-Heras, M.; García Lomillo, J.; Muñiz, P. Chemopreventive potential of powdered red wine pomace seasonings against colorectal cancer in HT-29 cells. J. Agric. Food Chem., 2017, 65(1), 66-73.
[] [PMID: 27957845]
Casanova, M.R.; Azevedo-Silva, J.; Rodrigues, L.R.; Preto, A. Colorectal cancer cells increase the production of short chain fatty acids by propionibacterium freudenreichii impacting on cancer cells survival. Front. Nutr., 2018, 5, 44.
[] [PMID: 29881727]
Chen, H.M.; Yu, Y.N.; Wang, J.L.; Lin, Y.W.; Kong, X.; Yang, C.Q.; Yang, L.; Liu, Z.J.; Yuan, Y.Z.; Liu, F.; Wu, J.X.; Zhong, L.; Fang, D.C.; Zou, W.; Fang, J.Y. Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. Am. J. Clin. Nutr., 2013, 97(5), 1044-1052.
[] [PMID: 23553152]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy