The development and progression of colorectal cancer (CRC), a major cause of cancer-related death in the western world, is accompanied with alterations of sphingolipid (SL) composition in colon tumors. A number of enzymes involved in the SL metabolism have been found to be deregulated in human colon tumors, in experimental rodent studies, and in human colon cancer cells in vitro. Therefore, the enzymatic pathways that modulate SL levels have received a significant attention, due to their possible contribution to CRC development, or as potential therapeutic targets. Many of these enzymes are associated with an increased sphingosine-1-phosphate/ceramide ratio, which is in turn linked with increased colon cancer cell survival, proliferation and cancer progression. Nevertheless, more attention should also be paid to the more complex SLs, including specific glycosphingolipids, such as lactosylceramides, which can be also deregulated during CRC development. In this review, we focus on the potential roles of individual SLs/SL metabolism enzymes in colon cancer, as well as on the pros and cons of employing the current in vitro models of colon cancer cells for lipidomic studies investigating the SL metabolism in CRC.

• Klíčová slova
• colon cancer (CRC) sphingolipidomics, colon cancer cells, colorectal cancer, glycosphingolipid, lactosylceramide, sphingolipid, sphingosine-1-phosphate,
• MeSH
• alkalická ceramidasa genetika   metabolismus   MeSH
• ceramidy metabolismus   MeSH
• fosfotransferasy s alkoholovou skupinou jako akceptorem genetika   metabolismus   MeSH
• kyselá ceramidasa genetika   metabolismus   MeSH
• laktosylceramidy metabolismus   MeSH
• lidé MeSH
• lysofosfolipidy metabolismus   MeSH
• metabolismus lipidů genetika   MeSH
• modely nemocí na zvířatech MeSH
• nádorové buňky kultivované MeSH
• nádory tračníku enzymologie   genetika   patologie   MeSH
• neutrální ceramidasa genetika   metabolismus   MeSH
• protoonkogenní proteiny c-akt genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• sfingolipidy metabolismus   MeSH
• sfingosin-N-acyltransferasa genetika   metabolismus   MeSH
• sfingosin analogy a deriváty   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ACER2 protein, human MeSH Prohlížeč
• alkalická ceramidasa MeSH
• ASAH1 protein, human MeSH Prohlížeč
• ASAH2 protein, human MeSH Prohlížeč
• ceramide 1-phosphate MeSH Prohlížeč
• ceramidy MeSH
• fosfotransferasy s alkoholovou skupinou jako akceptorem MeSH
• kyselá ceramidasa MeSH
• laktosylceramidy MeSH
• lysofosfolipidy MeSH
• neutrální ceramidasa MeSH
• protoonkogenní proteiny c-akt MeSH
• sfingolipidy MeSH
• sfingosin-N-acyltransferasa MeSH
• sfingosin MeSH
• sphingosine 1-phosphate MeSH Prohlížeč
• sphingosine kinase MeSH Prohlížeč

PURPOSE: Although beneficial effects of the dietary n-3 docosahexaenoic acid (DHA) or butyrate in colon carcinogenesis have been implicated, the mechanisms of their action are not fully clear. Here, we investigated modulations of composition of individual phospholipid (PL) classes, with a particular emphasis on cardiolipins (CLs), in colon cells treated with DHA, sodium butyrate (NaBt), or their combination (DHA/NaBt), and we evaluated possible associations between lipid changes and cell fate after fatty acid treatment. METHODS: In two distinct human colon cell models, foetal colon (FHC) and adenocarcinoma (HCT-116) cells, we compared patterns and composition of individual PL classes following the fatty acid treatment by HPLC-MS/MS. In parallel, we measured the parameters reflecting cell proliferation, differentiation and death. RESULTS: In FHC cells, NaBt induced primarily differentiation, while co-treatment with DHA shifted their response towards cell death. In contrast, NaBt induced apoptosis in HCT-116 cells, which was not further affected by DHA. DHA was incorporated in all main PL types, increasing their unsaturation, while NaBt did not additionally modulate these effects in either cell model. Nevertheless, we identified an unusually wide range of CL species to be highly increased by NaBt and particularly by DHA/NaBt, and these effects were more pronounced in HCT-116 cells. DHA and DHA/NaBt enhanced levels of high molecular weight and more unsaturated CL species, containing DHA, which was specific for either differentiation or apoptotic responses. CONCLUSIONS: We identified a wide range of CL species in the colon cells which composition was significantly modified after DHA and NaBt treatment. These specific CL modulations might contribute to distinct cellular differentiation or apoptotic responses.

• Klíčová slova
• Apoptosis, Butyrate, Cardiolipins, Colon cancer, Docosahexaenoic acid, Phospholipids,
• MeSH
• apoptóza účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• fosfolipidy chemie   MeSH
• HCT116 buňky MeSH
• kaspasa 3 genetika   metabolismus   MeSH
• kolon cytologie   účinky léků   MeSH
• kyselina máselná farmakologie   MeSH
• kyseliny dokosahexaenové farmakologie   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• proliferace buněk účinky léků   MeSH
• tandemová hmotnostní spektrometrie MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CASP3 protein, human MeSH Prohlížeč
• fosfolipidy MeSH
• kaspasa 3 MeSH
• kyselina máselná MeSH
• kyseliny dokosahexaenové MeSH

Intestinal homeostasis is precisely regulated by a number of endogenous regulatory molecules but significantly influenced by dietary compounds. Malfunction of this system may result in chronic inflammation and cancer. Dietary essential n-3 polyunsaturated fatty acids (PUFAs) and short-chain fatty acid butyrate produced from fibre display anti-inflammatory and anticancer activities. Both compounds were shown to modulate the production and activities of TNF family cytokines. Cytokines from the TNF family (TNF- α, TRAIL, and FasL) have potent inflammatory activities and can also regulate apoptosis, which plays an important role in cancer development. The results of our own research showed enhancement of apoptosis in colon cancer cells by a combination of either docosahexaenoic acid (DHA) or butyrate with TNF family cytokines, especially by promotion of the mitochondrial apoptotic pathway and modulation of NF κ B activity. This review is focused mainly on the interaction of dietary PUFAs and butyrate with these cytokines during colon inflammation and cancer development. We summarised recent knowledge about the cellular and molecular mechanisms involved in such effects and outcomes for intestinal cell behaviour and pathologies. Finally, the possible application for the prevention and therapy of colon inflammation and cancer is also outlined.

• MeSH
• apoptóza MeSH
• butyráty metabolismus   MeSH
• cytokiny metabolismus   MeSH
• dieta MeSH
• kolon patologie   MeSH
• kyseliny dokosahexaenové metabolismus   MeSH
• lidé MeSH
• mitochondrie patologie   MeSH
• myši MeSH
• nádory metabolismus   MeSH
• nenasycené mastné kyseliny metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• střevní sliznice metabolismus   MeSH
• tumor nekrotizující faktory metabolismus   MeSH
• zánět metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• butyráty MeSH
• cytokiny MeSH
• kyseliny dokosahexaenové MeSH
• nenasycené mastné kyseliny MeSH
• NF-kappa B MeSH
• tumor nekrotizující faktory MeSH