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.
2006
Vaculová, Alena; Hofmanová, Jirina; Soucek, Karel; Kozubík, Alois
In: FEBS letters, vol. 580, no. 28-29, pp. 6565–6569, 2006, ISSN: 0014-5793, (Place: England).
Abstract | Links | BibTeX | Tags: Apoptosis/*drug effects, Caspase 8/metabolism, Cell Survival/drug effects, Colonic Neoplasms/*pathology, Enzyme Activation/drug effects, Enzyme Inhibitors/pharmacology, Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors, Glycogen Synthase Kinase 3 beta, Glycogen Synthase Kinase 3/metabolism, HT29 Cells, Humans, Keratin-18/metabolism, Mitogen-Activated Protein Kinase 1/antagonists & inhibitors, Mitogen-Activated Protein Kinase 3/antagonists & inhibitors, Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins/metabolism, Phosphoinositide-3 Kinase Inhibitors, Phosphorylation/drug effects, Poly(ADP-ribose) Polymerases/metabolism, Proto-Oncogene Proteins c-akt/antagonists & inhibitors, Proto-Oncogene Proteins c-bcl-2/metabolism, TNF-Related Apoptosis-Inducing Ligand/*pharmacology
@article{vaculova_different_2006,
title = {Different modulation of TRAIL-induced apoptosis by inhibition of pro-survival pathways in TRAIL-sensitive and TRAIL-resistant colon cancer cells.},
author = {Alena Vaculová and Jirina Hofmanová and Karel Soucek and Alois Kozubík},
doi = {10.1016/j.febslet.2006.11.004},
issn = {0014-5793},
year = {2006},
date = {2006-12-01},
journal = {FEBS letters},
volume = {580},
number = {28-29},
pages = {6565–6569},
abstract = {Epithelial cells can be manipulated to undergo apoptosis depending on the balance between pro-survival and apoptotic signals. We showed that TRAIL-induced apoptosis may be differentially regulated by inhibitors of MEK ERK (U0126) or PI3K/Akt (LY294002) pathway in TRAIL-sensitive (HT-29) and TRAIL-resistant (SW620) human epithelial colon cancer cells. U0126 or LY294002 significantly enhanced TRAIL-induced apoptosis in HT-29 cells, but not in SW620 cells. We report a different regulation of the level of an anti-apoptotic Mcl-1 protein under MEK/ERK or PI3K/Akt pathway inhibition and suggest the mechanisms involved. A special attention was paid to the role of the ERK1/2, Akt, and glycogen synthase kinase 3beta.},
note = {Place: England},
keywords = {Apoptosis/*drug effects, Caspase 8/metabolism, Cell Survival/drug effects, Colonic Neoplasms/*pathology, Enzyme Activation/drug effects, Enzyme Inhibitors/pharmacology, Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors, Glycogen Synthase Kinase 3 beta, Glycogen Synthase Kinase 3/metabolism, HT29 Cells, Humans, Keratin-18/metabolism, Mitogen-Activated Protein Kinase 1/antagonists & inhibitors, Mitogen-Activated Protein Kinase 3/antagonists & inhibitors, Mitogen-Activated Protein Kinase Kinases/antagonists & inhibitors, Myeloid Cell Leukemia Sequence 1 Protein, Neoplasm Proteins/metabolism, Phosphoinositide-3 Kinase Inhibitors, Phosphorylation/drug effects, Poly(ADP-ribose) Polymerases/metabolism, Proto-Oncogene Proteins c-akt/antagonists & inhibitors, Proto-Oncogene Proteins c-bcl-2/metabolism, TNF-Related Apoptosis-Inducing Ligand/*pharmacology},
pubstate = {published},
tppubtype = {article}
}
Epithelial cells can be manipulated to undergo apoptosis depending on the balance between pro-survival and apoptotic signals. We showed that TRAIL-induced apoptosis may be differentially regulated by inhibitors of MEK ERK (U0126) or PI3K/Akt (LY294002) pathway in TRAIL-sensitive (HT-29) and TRAIL-resistant (SW620) human epithelial colon cancer cells. U0126 or LY294002 significantly enhanced TRAIL-induced apoptosis in HT-29 cells, but not in SW620 cells. We report a different regulation of the level of an anti-apoptotic Mcl-1 protein under MEK/ERK or PI3K/Akt pathway inhibition and suggest the mechanisms involved. A special attention was paid to the role of the ERK1/2, Akt, and glycogen synthase kinase 3beta.