2019
Zapletal, Ondřej; Procházková, Jiřina; Dubec, Vít; Hofmanová, Jiřina; Kozubík, Alois; Vondráček, Jan
In: Toxicology, vol. 412, pp. 1–11, 2019, ISSN: 1879-3185 0300-483X, (Place: Ireland).
Abstract | Links | BibTeX | Tags: Benzo(a)pyrene/*toxicity, Butyrate, Butyrates/*pharmacology, Carcinogens/*toxicity, Cell Line, Colon epithelium, Colon/cytology, Epithelial Cells/drug effects/metabolism, Humans, N-acetyltransferases, NAD(P)H:quinone oxidoreductase 1, Oxidoreductases/genetics/*metabolism, Polycyclic aromatic hydrocarbons, Transferases/genetics/*metabolism, UDP-glucuronosyltransferases, Xenobiotics/metabolism
@article{zapletal_butyrate_2019,
title = {Butyrate interacts with benzo[a]pyrene to alter expression and activities of xenobiotic metabolizing enzymes involved in metabolism of carcinogens within colon epithelial cell models.},
author = {Ondřej Zapletal and Jiřina Procházková and Vít Dubec and Jiřina Hofmanová and Alois Kozubík and Jan Vondráček},
doi = {10.1016/j.tox.2018.11.001},
issn = {1879-3185 0300-483X},
year = {2019},
date = {2019-01-01},
journal = {Toxicology},
volume = {412},
pages = {1–11},
abstract = {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.},
note = {Place: Ireland},
keywords = {Benzo(a)pyrene/*toxicity, Butyrate, Butyrates/*pharmacology, Carcinogens/*toxicity, Cell Line, Colon epithelium, Colon/cytology, Epithelial Cells/drug effects/metabolism, Humans, N-acetyltransferases, NAD(P)H:quinone oxidoreductase 1, Oxidoreductases/genetics/*metabolism, Polycyclic aromatic hydrocarbons, Transferases/genetics/*metabolism, UDP-glucuronosyltransferases, Xenobiotics/metabolism},
pubstate = {published},
tppubtype = {article}
}
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.
2018
Tylichová, Zuzana; Slavík, Josef; Ciganek, Miroslav; Ovesná, Petra; Krčmář, Pavel; Straková, Nicol; Machala, Miroslav; Kozubík, Alois; Hofmanová, Jiřina; Vondráček, Jan
Butyrate and docosahexaenoic acid interact in alterations of specific lipid classes in differentiating colon cancer cells. Journal Article
In: Journal of cellular biochemistry, vol. 119, no. 6, pp. 4664–4679, 2018, ISSN: 1097-4644 0730-2312, (Place: United States).
Abstract | Links | BibTeX | Tags: Apoptosis/*drug effects, Butyrate, Butyrates/*pharmacology, Cell Differentiation/*drug effects, Ceramides, Colon cancer, Colonic Neoplasms/*metabolism/pathology, Docosahexaenoic acid, Docosahexaenoic Acids/*pharmacology, HCT116 Cells, Humans, lipid analyses, Lipid Metabolism/*drug effects, Membrane Lipids/classification/*metabolism, Phospholipids
@article{tylichova_butyrate_2018,
title = {Butyrate and docosahexaenoic acid interact in alterations of specific lipid classes in differentiating colon cancer cells.},
author = {Zuzana Tylichová and Josef Slavík and Miroslav Ciganek and Petra Ovesná and Pavel Krčmář and Nicol Straková and Miroslav Machala and Alois Kozubík and Jiřina Hofmanová and Jan Vondráček},
doi = {10.1002/jcb.26641},
issn = {1097-4644 0730-2312},
year = {2018},
date = {2018-06-01},
journal = {Journal of cellular biochemistry},
volume = {119},
number = {6},
pages = {4664–4679},
abstract = {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.},
note = {Place: United States},
keywords = {Apoptosis/*drug effects, Butyrate, Butyrates/*pharmacology, Cell Differentiation/*drug effects, Ceramides, Colon cancer, Colonic Neoplasms/*metabolism/pathology, Docosahexaenoic acid, Docosahexaenoic Acids/*pharmacology, HCT116 Cells, Humans, lipid analyses, Lipid Metabolism/*drug effects, Membrane Lipids/classification/*metabolism, Phospholipids},
pubstate = {published},
tppubtype = {article}
}
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.
2017
Tylichová, Zuzana; Straková, Nicol; Vondráček, Jan; Vaculová, Alena Hyršlová; Kozubík, Alois; Hofmanová, Jiřina
In: The Journal of nutritional biochemistry, vol. 39, pp. 145–155, 2017, ISSN: 1873-4847 0955-2863, (Place: United States).
Abstract | Links | BibTeX | Tags: Antineoplastic Agents/pharmacology, Apoptosis/*drug effects, Autophagy, Autophagy/*drug effects, Butyrate, Butyrates/*pharmacology, Butyric Acid/pharmacology, Caspase 3/genetics/metabolism, Cell Differentiation/drug effects, Colon cancer, Colonic Neoplasms/*pathology, Differentiation, Docosahexaenoic acid, Docosahexaenoic Acids/*pharmacology, HCT116 Cells, HT29 Cells, Humans, Mitochondria/drug effects/metabolism, PPAR gamma/genetics/*metabolism, PPARγ
@article{tylichova_activation_2017,
title = {Activation of autophagy and PPARγ protect colon cancer cells against apoptosis induced by interactive effects of butyrate and DHA in a cell type-dependent manner: The role of cell differentiation.},
author = {Zuzana Tylichová and Nicol Straková and Jan Vondráček and Alena Hyršlová Vaculová and Alois Kozubík and Jiřina Hofmanová},
doi = {10.1016/j.jnutbio.2016.09.006},
issn = {1873-4847 0955-2863},
year = {2017},
date = {2017-01-01},
journal = {The Journal of nutritional biochemistry},
volume = {39},
pages = {145–155},
abstract = {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.},
note = {Place: United States},
keywords = {Antineoplastic Agents/pharmacology, Apoptosis/*drug effects, Autophagy, Autophagy/*drug effects, Butyrate, Butyrates/*pharmacology, Butyric Acid/pharmacology, Caspase 3/genetics/metabolism, Cell Differentiation/drug effects, Colon cancer, Colonic Neoplasms/*pathology, Differentiation, Docosahexaenoic acid, Docosahexaenoic Acids/*pharmacology, HCT116 Cells, HT29 Cells, Humans, Mitochondria/drug effects/metabolism, PPAR gamma/genetics/*metabolism, PPARγ},
pubstate = {published},
tppubtype = {article}
}
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.