Butyrate and docosahexaenoic acid interact in alterations of specific lipid classes in differentiating colon cancer cells

Tylichová, Zuzana; Slavík, Josef; Cigánek, Miroslav; Ovesná, Petra; Krčmář, Pavel; Straková, Nicol; Machala, Miroslav; Kozubı́k, Alois; Hofmanová, Jiřina; Vondráček, Jan

doi:10.1002/jcb.26641

Cited by 13 publications

(16 citation statements)

References 52 publications

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“…Laboratory tests on a human colon cancer cell line confirmed that the administration of exogenous C16-Cer promoted programmed cell death, and it was suggested that maybe an increase of endogenous production of C16-Cer may also exert similar effects [25]. However, the biological activity of the same ceramide analogs in different types of histological tissues may be completely different.…”

Section: Discussionmentioning

confidence: 99%

Ceramides Profile Identifies Patients with More Advanced Stages of Colorectal Cancer

Markowski¹,

Błachnio-Zabielska

Guzińska‐Ustymowicz

et al. 2020

Biomolecules

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Much attention is paid to different sphingolipid pathways because of their possible use in diagnostics and treatment. However, the activity status and significance of ceramide pathways in colorectal cancer are still unclear. We analyzed colorectal cancer patients to evaluate sphingolipid profiles in the blood, colorectal cancer (CRC) tissues, and healthy surrounding colorectal tissues of the same patient, simultaneously, using liquid chromatography coupled with triple quadrupole mass spectrometry. Furthermore, we measured protein expression of de novo ceramide synthesis enzymes and mitochondrial markers in tissues using western blot. We confirmed the different sphingolipid contents in colorectal cancer tissue compared to healthy surrounding tissues. Furthermore, we showed changed amounts of several ceramides in more advanced colorectal cancer tissue and found a prominently higher circulating level of several of them. Moreover, we observed a relationship between the amounts of some ceramide species in colorectal cancer tissue and plasma depending on the stage of colorectal cancer according to TNM (tumors, nodes, metastasis) classification. We think that the combined measurement of several ceramide concentrations in plasma can help distinguish early-stage lesions from advanced colorectal cancer and can help produce a screening test to detect early colorectal cancer.

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Section: Discussionmentioning

confidence: 99%

Ceramides Profile Identifies Patients with More Advanced Stages of Colorectal Cancer

Markowski¹,

Błachnio-Zabielska

Guzińska‐Ustymowicz

et al. 2020

Biomolecules

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“…While upregulation of Cer 16:0 contributes to the induction of apoptosis in human colon cancer cells, increased Cer 24:1 levels are, in contrast, associated with cell survival [13]. Certain Cer species (16:0 and 24:1), as well as modulations of hexosylCer (HexCer) 24:1 and sphingomyelin (SM) 24:1 levels, could thus play significant roles in colon cancer cell life/death decisions, for example in response to therapeutic agents in vitro [14], or during the switch of cellular response of CRC-derived cell lines from differentiation to apoptosis [15].…”

Section: Currently Known Role(s) Of Sls In Colon Cancer Cells—an Omentioning

confidence: 99%

“…Both CERS5 and 6, as well as their product, Cer 16:0, have also been shown to regulate post-mitochondrial cell death [25]. In this context, it is perhaps interesting that we have previously observed that induction of apoptosis in differentiating colon cancer cells is associated with up-regulation of CERS5 (which contributes primarily to Cer 16:0 production) and down-regulation of CERS2 (which contributes to Cer 24:1 production), as well as with deregulation of expression of other SL metabolism enzymes, namely with induction of sphingomyelin phosphodiesterase 1 (SMPD1) and down-regulation of dihydroceramide desaturase 2 (DEGS2) [15].…”

Section: Currently Known Role(s) Of Sls In Colon Cancer Cells—an Omentioning

confidence: 99%

“…These results have suggested that mutual interactions may exist between cellular lipidome and environmental factors, including dietary lipids, which may thus substantially alter cellular responses (apoptosis, differentiation) to treatment. Here, the cell transformation stage, as well as distinct differentiation capacities of colon cancer cells, seem to play important roles [14,15,66,67].…”

Section: Lipidomic Analyses Of Human In Vitro Models Of Colon Cancmentioning

confidence: 99%

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Colon Cancer and Perturbations of the Sphingolipid Metabolism

Machala

Procházková

Hofmanová

et al. 2019

IJMS

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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.

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“…Tylichova et al investigated the effect of sodium butyrate (NaBt) in vitro and showed that NaBt alters the cellular lipidome in human colon cancer cells. Amongst others, it leads to an increase of C16:0-ceramide and enhanced ceramide synthase (CerS) 5 expression [ 5 ]. Additionally in human colitis patients, we were previously able to show that ceramides and CerS are significantly deregulated in dependency of the disease score in colon as well as in white blood cells [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Ceramide Synthase 5 Deficiency Aggravates Dextran Sodium Sulfate-Induced Colitis and Colon Carcinogenesis and Impairs T-Cell Activation

El-Hindi

Brachtendorf

Hartel

et al. 2020

Cancers

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Ceramide synthase 5 is one of six enzymes that catalyze the production of ceramides from sphingosine or sphinganine. Ceramides are important components of cell membranes and act as signaling molecules. Previously it has been shown that ceramide synthase 6 and 2 influence colitis in several animal models with sometimes opposite effects. Here, we investigated the disease course of dextran sodium sulfate-induced acute colitis and azoxymethane/dextran sodium sulfate-induced colitis-associated colon cancer in mice with global ceramide synthase 5 knockout (CerS5-ko) or with ceramide synthase 5 knockout restricted to the colon epithelium (CerS5fl/fl VilCre). We monitored disease development and analyzed colon barrier function as well as the immune cell status in these mice. CerS5-ko mice but not CerS5fl/fl-VilCre mice were more susceptible to acute and chronic inflammation. However, the cell barrier function of colon epithelial cells was not disturbed by downregulation of ceramide synthase 5. Instead, untreated CerS5-ko mice displayed reduced numbers of CD3+ immune cells in the spleen, colon, and blood, especially of intraepithelial CD8+ T-cells, which was not obvious in CerS5fl/fl Vil Cre mice. Reduced T-cell number in colon tissue of CerS5-ko mice was accompanied by a reduced expression of IL-1β, IFNγ, and IL-4. In vitro investigations revealed that knockdown of ceramide synthase 5 in T-cells impaired T-cell activation. In summary, we show that CerS5-ko mice were more susceptible to dextran sodium sulfate-induced colitis and azoxymethane/dextran sodium sulfate-induced colitis-associated colon cancer. A reduced number of T-cells in the colon epithelium that was already the case in untreated CerS5-ko mice might have contributed to this effect.

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Butyrate and docosahexaenoic acid interact in alterations of specific lipid classes in differentiating colon cancer cells

Cited by 13 publications

References 52 publications

Ceramides Profile Identifies Patients with More Advanced Stages of Colorectal Cancer

Ceramides Profile Identifies Patients with More Advanced Stages of Colorectal Cancer

Colon Cancer and Perturbations of the Sphingolipid Metabolism

Ceramide Synthase 5 Deficiency Aggravates Dextran Sodium Sulfate-Induced Colitis and Colon Carcinogenesis and Impairs T-Cell Activation

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