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.

• Keywords
• colon cancer (CRC) sphingolipidomics, colon cancer cells, colorectal cancer, glycosphingolipid, lactosylceramide, sphingolipid, sphingosine-1-phosphate,
• MeSH
• Alkaline Ceramidase genetics   metabolism   MeSH
• Ceramides metabolism   MeSH
• Phosphotransferases (Alcohol Group Acceptor) genetics   metabolism   MeSH
• Acid Ceramidase genetics   metabolism   MeSH
• Lactosylceramides metabolism   MeSH
• Humans MeSH
• Lysophospholipids metabolism   MeSH
• Lipid Metabolism genetics   MeSH
• Disease Models, Animal MeSH
• Tumor Cells, Cultured MeSH
• Colonic Neoplasms enzymology   genetics   pathology   MeSH
• Neutral Ceramidase genetics   metabolism   MeSH
• Proto-Oncogene Proteins c-akt genetics   metabolism   MeSH
• Gene Expression Regulation, Neoplastic * MeSH
• Sphingolipids metabolism   MeSH
• Sphingosine N-Acyltransferase genetics   metabolism   MeSH
• Sphingosine analogs & derivatives   metabolism   MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH
• Names of Substances
• ACER2 protein, human MeSH Browser
• Alkaline Ceramidase MeSH
• ASAH1 protein, human MeSH Browser
• ASAH2 protein, human MeSH Browser
• ceramide 1-phosphate MeSH Browser
• Ceramides MeSH
• Phosphotransferases (Alcohol Group Acceptor) MeSH
• Acid Ceramidase MeSH
• Lactosylceramides MeSH
• Lysophospholipids MeSH
• Neutral Ceramidase MeSH
• Proto-Oncogene Proteins c-akt MeSH
• Sphingolipids MeSH
• Sphingosine N-Acyltransferase MeSH
• Sphingosine MeSH
• sphingosine 1-phosphate MeSH Browser
• sphingosine kinase MeSH Browser

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.

• Keywords
• Apoptosis, Butyrate, Cardiolipins, Colon cancer, Docosahexaenoic acid, Phospholipids,
• MeSH
• Apoptosis drug effects   MeSH
• Cell Differentiation drug effects   MeSH
• Phospholipids chemistry   MeSH
• HCT116 Cells MeSH
• Caspase 3 genetics   metabolism   MeSH
• Colon cytology   drug effects   MeSH
• Butyric Acid pharmacology   MeSH
• Docosahexaenoic Acids pharmacology   MeSH
• Humans MeSH
• Cell Line, Tumor MeSH
• Cell Proliferation drug effects   MeSH
• Tandem Mass Spectrometry MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• CASP3 protein, human MeSH Browser
• Phospholipids MeSH
• Caspase 3 MeSH
• Butyric Acid MeSH
• Docosahexaenoic Acids MeSH