The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM+ cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.

• Klíčová slova
• EpCAM, colorectal carcinoma, desaturation, epithelial cells, fatty acid synthesis, lipidomics, lysophospholipids, phospholipids,
• MeSH
• adenokarcinom enzymologie   genetika   metabolismus   MeSH
• desaturasy mastných kyselin genetika   metabolismus   MeSH
• elongasy mastných kyselin genetika   metabolismus   MeSH
• epitelové buňky enzymologie   metabolismus   MeSH
• fosfolipidy metabolismus   MeSH
• lidé MeSH
• lipidomika MeSH
• lipogeneze MeSH
• mastné kyseliny metabolismus   MeSH
• metabolismus lipidů * MeSH
• nádory tračníku enzymologie   genetika   metabolismus   MeSH
• regulace genové exprese u nádorů * MeSH
• senioři MeSH
• stearyl-CoA-desaturasa genetika   metabolismus   MeSH
• syntázy mastných kyselin genetika   metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• desaturasy mastných kyselin MeSH
• elongasy mastných kyselin MeSH
• ELOVL5 protein, human MeSH Prohlížeč
• FADS2 protein, human MeSH Prohlížeč
• fosfolipidy MeSH
• mastné kyseliny MeSH
• stearyl-CoA-desaturasa MeSH
• syntázy mastných kyselin MeSH

• Klíčová slova
• B4GALTs, Colon adenocarcinoma, EPCAM-positive cells, Lactosylceramide, Sphingolipid metabolism,
• MeSH
• adhezní molekula epiteliálních buněk metabolismus   MeSH
• dospělí MeSH
• galaktosyltransferasy genetika   MeSH
• kolorektální nádory metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• sfingolipidy metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adhezní molekula epiteliálních buněk MeSH
• EPCAM protein, human MeSH Prohlížeč
• galaktosyltransferasy MeSH
• sfingolipidy MeSH

Identification of changes of phospholipid (PL) composition occurring during colorectal cancer (CRC) development may help us to better understand their roles in CRC cells. Here, we used LC-MS/MS-based PL profiling of cell lines derived from normal colon mucosa, or isolated at distinct stages of CRC development, in order to study alterations of PL species potentially linked with cell transformation. We found that a detailed evaluation of phosphatidylinositol (PI) and phosphatidylserine (PS) classes allowed us to cluster the studied epithelial cell lines according to their origin: i) cells originally derived from normal colon tissue (NCM460, FHC); ii) cell lines derived from colon adenoma or less advanced differentiating adenocarcinoma cells (AA/C1, HT-29); or, iii) cells obtained by in vitro transformation of adenoma cells and advanced colon adenocarcinoma cells (HCT-116, AA/C1/SB10, SW480, SW620). Although we tentatively identified several PS and PI species contributing to cell line clustering, full PI and PS profiles appeared to be a key to the successful cell line discrimination. In parallel, we compared PL composition of primary epithelial (EpCAM-positive) cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients, with PL profiles of cell lines derived from normal colon mucosa (NCM460) and from colon adenocarcinoma (HCT-116, SW480) cells, respectively. In general, higher total levels of all PL classes were observed in tumor cells. The overall PL profiles of the cell lines, when compared with the respective patient-derived cells, exhibited similarities. Nevertheless, there were also some notable differences in levels of individual PL species. This indicated that epithelial cell lines, derived either from normal colon tissue or from CRC cells, could be employed as models for functional lipidomic analyses of colon cells, albeit with some caution. The biological significance of the observed PL deregulation, or their potential links with specific CRC stages, deserve further investigation.

• MeSH
• analýza hlavních komponent MeSH
• epitelové buňky metabolismus   patologie   MeSH
• fosfolipidy metabolismus   MeSH
• kolon patologie   MeSH
• lidé MeSH
• lipidomika * MeSH
• nádorové buněčné linie MeSH
• nádory tračníku metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• fosfolipidy MeSH

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

Dietary carcinogens, such as benzo[a]pyrene (BaP), are suspected to contribute to colorectal cancer development. n-3 Polyunsaturated fatty acids (PUFAs) decrease colorectal cancer risk in individuals consuming diets rich in PUFAs. Here, we investigated the impact of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid on metabolism and genotoxicity of BaP in human cell models derived from the colon: HT-29 and HCT-116 cell lines. Both PUFAs reduced levels of excreted BaP metabolites, in particular BaP-tetrols and hydroxylated BaP metabolites, as well as formation of DNA adducts in HT-29 and HCT-116 cells. However, EPA appeared to be a more potent inhibitor of formation of some intracellular BaP metabolites, including BaP-7,8-dihydrodiol. EPA also reduced phosphorylation of histone H2AX (Ser139) in HT-29 cells, which indicated that it may reduce further forms of DNA damage, including DNA double strand breaks. Both PUFAs inhibited induction of CYP1 activity in colon cells determined as 7-ethoxyresorufin-O-deethylase (EROD); this was at least partly linked with inhibition of induction of CYP1A1, 1A2 and 1B1 mRNAs. The downregulation and/or inhibition of CYP1 enzymes by PUFAs could thus alter metabolism and reduce genotoxicity of BaP in human colon cells, which might contribute to known chemopreventive effects of PUFAs in colon epithelium.

• Klíčová slova
• Colon cancer, DNA damage, Docosahexaenoic acid, Eicosapentaenoic acid, Polycyclic aromatic hydrocarbon,
• MeSH
• adukty DNA metabolismus   MeSH
• antikarcinogenní látky farmakologie   MeSH
• benzopyren škodlivé účinky   metabolismus   MeSH
• epitelové buňky účinky léků   MeSH
• histony metabolismus   MeSH
• kontrolní body fáze S buněčného cyklu účinky léků   MeSH
• kyselina eikosapentaenová farmakologie   MeSH
• kyseliny dokosahexaenové farmakologie   MeSH
• lidé MeSH
• mutageny škodlivé účinky   metabolismus   MeSH
• nádorové buněčné linie MeSH
• poškození DNA účinky léků   MeSH
• rodina 1 cytochromu P450 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adukty DNA MeSH
• antikarcinogenní látky MeSH
• benzopyren MeSH
• H2AX protein, human MeSH Prohlížeč
• histony MeSH
• kyselina eikosapentaenová MeSH
• kyseliny dokosahexaenové MeSH
• mutageny MeSH
• rodina 1 cytochromu P450 MeSH

Butyrate helps to maintain colon homeostasis and exhibits chemopreventive effects in colon epithelium. We examined the interactive effects of butyrate and benzo[a]pyrene (BaP), dietary carcinogen, in regulation of expression of a panel of phase I and II xenobiotic metabolizing enzymes (XMEs) in human colon cells. In human colon carcinoma HCT-116 and HT-29 cell lines, butyrate alone increased mRNA levels of some enzymes, such as N-acetyltransferases (in particular NAT2). In combination with BaP, butyrate potentiated induction of cytochrome P450 family 1 enzymes (CYP1A1), aldo-keto reductases (AKR1C1) or UDP-glucuronosyltransferases (UGT1A1). There were some notable differences between cell lines, as butyrate potentiated induction of NAD(P)H:quinone oxidoreductase 1 (NQO1) and UGT1A4 only in HCT-116 cells, and it even repressed AKR1C3 induction in HT-29 cells. Butyrate also promoted induction of CYP1, NQO1, NAT2, UGT1A1 or UGT1A4 in human colon Caco-2 cells, in a differentiation-dependent manner. Differentiated Caco-2 cells exhibited a higher inducibility of selected XME genes than undifferentiated cells. Butyrate increased induction of enzymatic activities of NATs, NQO1 and UGTs by BaP in HCT-116 and HT29 cells, whereas in differentiated Caco-2 cells it helped to increase only enzymatic activity of NQO1 and UGTs. Together, the present data suggest that butyrate may modulate expression/activities of several enzymes involved in metabolism of carcinogens in colon. In some cases (NAT2, UGT1 A1), this was linked to inhibition of histone deacetylases (HDAC), as confirmed by using HDAC inhibitor trichostatin A. These results may have implications for our understanding of the role of butyrate in regulation of XMEs and carcinogen metabolism in colon.

• Klíčová slova
• Butyrate, Colon epithelium, N-acetyltransferases, NAD(P)H:quinone oxidoreductase 1, Polycyclic aromatic hydrocarbons, UDP-glucuronosyltransferases,
• MeSH
• benzopyren toxicita   MeSH
• buněčné linie MeSH
• butyráty farmakologie   MeSH
• epitelové buňky účinky léků   metabolismus   MeSH
• karcinogeny toxicita   MeSH
• kolon cytologie   MeSH
• lidé MeSH
• oxidoreduktasy genetika   metabolismus   MeSH
• transferasy genetika   metabolismus   MeSH
• xenobiotika metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• benzopyren MeSH
• butyráty MeSH
• karcinogeny MeSH
• oxidoreduktasy MeSH
• transferasy MeSH
• xenobiotika MeSH

Docosahexaenoic acid (DHA) and sodium butyrate (NaBt) exhibit a number of interactive effects on colon cancer cell growth, differentiation, or apoptosis; however, the molecular mechanisms responsible for these interactions and their impact on cellular lipidome are still not fully clear. Here, we show that both dietary agents together induce dynamic alterations of lipid metabolism, specific cellular lipid classes, and fatty acid composition. In HT-29 cell line, a model of differentiating colon carcinoma cells, NaBt supported incorporation of free DHA into non-polar lipids and their accumulation in cytoplasmic lipid droplets. DHA itself was not incorporated into sphingolipids; however, it significantly altered representation of individual ceramide (Cer) classes, in particular in combination with NaBt (DHA/NaBt). We observed altered expression of enzymes involved in Cer metabolism in cells treated with NaBt or DHA/NaBt, and exogenous Cer 16:0 was found to promote induction of apoptosis in differentiating HT-29 cells. NaBt, together with DHA, increased n-3 fatty acid synthesis and attenuated metabolism of monounsaturated fatty acids. Finally, DHA and/or NaBt altered expression of proteins involved in synthesis of fatty acids, including elongase 5, stearoyl CoA desaturase 1, or fatty acid synthase, with NaBt increasing expression of caveolin-1 and CD36 transporter, which may further promote DHA incorporation and its impact on cellular lipidome. In conclusion, our results indicate that interactions of DHA and NaBt exert complex changes in cellular lipidome, which may contribute to the alterations of colon cancer cell differentiation/apoptotic responses. The present data extend our knowledge about the nature of interactive effects of dietary fatty acids.

• Klíčová slova
• butyrate, ceramides, colon cancer, docosahexaenoic acid, lipid analyses, phospholipids,
• MeSH
• apoptóza účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• butyráty farmakologie   MeSH
• HCT116 buňky MeSH
• kyseliny dokosahexaenové farmakologie   MeSH
• lidé MeSH
• membránové lipidy klasifikace   metabolismus   MeSH
• metabolismus lipidů účinky léků   MeSH
• nádory tračníku metabolismus   patologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• butyráty MeSH
• kyseliny dokosahexaenové MeSH
• membránové lipidy MeSH

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

Butyrate, a short-chain fatty acid produced by fermentation of dietary fiber, is an important regulator of colonic epithelium homeostasis. In this study, we investigated the impact of this histone deacetylase (HDAC) inhibitor on expression/activity of cytochrome P450 family 1 (CYP1) and on metabolism of carcinogenic polycyclic aromatic hydrocarbon, benzo[a]pyrene (BaP), in colon epithelial cells. Sodium butyrate (NaBt) strongly potentiated the BaP-induced expression of CYP1A1 in human colon carcinoma HCT116 cells. It also co-stimulated the 7-ethoxyresorufin-O-deethylase (EROD) activity induced by the 2,3,7,8-tetrachlorodibenzo-p-dioxin, a prototypical ligand of the aryl hydrocarbon receptor. Up-regulation of CYP1A1 expression/activity corresponded with an enhanced metabolism of BaP and formation of covalent DNA adducts. NaBt significantly potentiated CYP1A1 induction and/or metabolic activation of BaP also in other human colon cell models, colon adenoma AA/C1 cells, colon carcinoma HT-29 cells, or in NCM460D cell line derived from normal colon mucosa. Our results suggest that the effects of NaBt were due to its impact on histone acetylation, because additional HDAC inhibitors (trichostatin A and suberanilohydroxamic acid) likewise increased both the induction of EROD activity and formation of covalent DNA adducts. NaBt-induced acetylation of histone H3 (at Lys14) and histone H4 (at Lys16), two histone modifications modulated during activation of CYP1A1 transcription, and it reduced binding of HDAC1 to the enhancer region of CYP1A1 gene. This in vitro study suggests that butyrate, through modulation of histone acetylation, may potentiate induction of CYP1A1 expression, which might in turn alter the metabolism of BaP within colon epithelial cells.

• Klíčová slova
• Butyrate, CYP1A1, Colon epithelial cells, DNA adducts, Histone deacetylases, Polycyclic aromatic hydrocarbons,
• MeSH
• adukty DNA účinky léků   metabolismus   MeSH
• benzopyren metabolismus   farmakokinetika   MeSH
• beta-katenin metabolismus   MeSH
• buňky HT-29 MeSH
• cytochrom P-450 CYP1A1 genetika   metabolismus   MeSH
• HCT116 buňky MeSH
• histondeacetylasa 1 antagonisté a inhibitory   metabolismus   MeSH
• histony metabolismus   MeSH
• inhibitory histondeacetylas farmakologie   MeSH
• kolon účinky léků   metabolismus   MeSH
• kyselina máselná farmakologie   MeSH
• lidé MeSH
• metabolická inaktivace MeSH
• zesilovače transkripce účinky léků   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adukty DNA MeSH
• benzopyren MeSH
• beta-katenin MeSH
• CTNNB1 protein, human MeSH Prohlížeč
• CYP1A1 protein, human MeSH Prohlížeč
• cytochrom P-450 CYP1A1 MeSH
• HDAC1 protein, human MeSH Prohlížeč
• histondeacetylasa 1 MeSH
• histony MeSH
• inhibitory histondeacetylas MeSH
• kyselina máselná MeSH

The short-chain and n-3 polyunsaturated fatty acids exhibit anticancer properties, and they may mutually interact within the colon. However, the molecular mechanisms of their action in colon cancer cells are still not fully understood. Our study focused on the mechanisms responsible for the diverse effects of sodium butyrate (NaBt), in particular when interacting with docosahexaenoic acid (DHA), in distinct colon cancer cell types, in which NaBt either induces cell differentiation or activates programmed cell death involving mitochondrial pathway. NaBt activated autophagy both in HT-29 cells, which are sensitive to induction of differentiation, and in nondifferentiating HCT-116 cells. However, autophagy supported cell survival only in HT-29 cells. Combination of NaBt with DHA-promoted cell death, especially in HCT-116 cells and after longer time intervals. The inhibition of autophagy both attenuated differentiation and enhanced apoptosis in HT-29 cells treated with NaBt and DHA, but it had no effect in HCT-116 cells. NaBt, especially in combination with DHA, activated PPARγ in both cell types. PPARγ silencing decreased differentiation and increased apoptosis only in HT-29 cells, therefore we verified the role of caspases in apoptosis, differentiation and also PPARγ activity using a pan-caspase inhibitor. In summary, our data suggest that diverse responses of colon cancer cells to fatty acids may rely on their sensitivity to differentiation, which may in turn depend on distinct engagement of autophagy, caspases and PPARγ. These results contribute to understanding of mechanisms underlying differential effects of NaBt, when interacting with other dietary fatty acids, in colon cancer cells.

• Klíčová slova
• Autophagy, Butyrate, Colon cancer, Differentiation, Docosahexaenoic acid, PPARγ,
• MeSH
• apoptóza účinky léků   MeSH
• autofagie účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• buňky HT-29 MeSH
• butyráty farmakologie   MeSH
• HCT116 buňky MeSH
• kaspasa 3 genetika   metabolismus   MeSH
• kyselina máselná farmakologie   MeSH
• kyseliny dokosahexaenové farmakologie   MeSH
• lidé MeSH
• mitochondrie účinky léků   metabolismus   MeSH
• nádory tračníku patologie   MeSH
• PPAR gama genetika   metabolismus   MeSH
• protinádorové látky farmakologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• butyráty MeSH
• CASP3 protein, human MeSH Prohlížeč
• kaspasa 3 MeSH
• kyselina máselná MeSH
• kyseliny dokosahexaenové MeSH
• PPAR gama MeSH
• protinádorové látky MeSH