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.
2008
Ondrousková, Eva; Soucek, Karel; Horváth, Viktor; Smarda, Jan
Alternative pathways of programmed cell death are activated in cells with defective caspase-dependent apoptosis. Journal Article
In: Leukemia research, vol. 32, no. 4, pp. 599–609, 2008, ISSN: 0145-2126, (Place: England).
Abstract | Links | BibTeX | Tags: Animals, Antineoplastic Agents/*pharmacology, Apoptosis/*drug effects, Arsenic Trioxide, Arsenicals/pharmacology, Autophagy/*drug effects, Blotting, Camptothecin/pharmacology, Caspases/*metabolism, Cell Line, Cell Transformation, Chickens, Cycloheximide/pharmacology, Fluorescence, Genes, Humans, Microscopy, myb/physiology, Necrosis, Neoplastic/*pathology, Oxides/pharmacology, Signal Transduction/*drug effects, Transformed, U937 Cells/drug effects, Western
@article{ondrouskova_alternative_2008,
title = {Alternative pathways of programmed cell death are activated in cells with defective caspase-dependent apoptosis.},
author = {Eva Ondrousková and Karel Soucek and Viktor Horváth and Jan Smarda},
doi = {10.1016/j.leukres.2007.05.012},
issn = {0145-2126},
year = {2008},
date = {2008-04-01},
journal = {Leukemia research},
volume = {32},
number = {4},
pages = {599–609},
abstract = {Loss of programmed cell death pathways is one of the features of malignancy that complicate the response of cancer cells to a therapy. Activation of alternative cell death pathways offers a promising approach to enhance efficiency of cancer chemotherapy. We analysed programmed cell death pathways of v-myb-transformed BM2 monoblasts induced by arsenic trioxide, cycloheximide and camptothecin with U937 promonocytes as a reference cell line. We show that induced death of BM2 cells is not executed by caspases but rather by alternative cell death pathways. Camptothecin induces the lysosome-dependent cell death, arsenic trioxide induces autophagy, and most of cycloheximide-treated BM2 cells die by necrosis. The fact that alternative cell death pathways can be switched in cells with defects in activation and/or function of caspases suggests that understanding and targeting of these pathways could improve therapy of cancer cells suffering from defective apoptosis.},
note = {Place: England},
keywords = {Animals, Antineoplastic Agents/*pharmacology, Apoptosis/*drug effects, Arsenic Trioxide, Arsenicals/pharmacology, Autophagy/*drug effects, Blotting, Camptothecin/pharmacology, Caspases/*metabolism, Cell Line, Cell Transformation, Chickens, Cycloheximide/pharmacology, Fluorescence, Genes, Humans, Microscopy, myb/physiology, Necrosis, Neoplastic/*pathology, Oxides/pharmacology, Signal Transduction/*drug effects, Transformed, U937 Cells/drug effects, Western},
pubstate = {published},
tppubtype = {article}
}
Loss of programmed cell death pathways is one of the features of malignancy that complicate the response of cancer cells to a therapy. Activation of alternative cell death pathways offers a promising approach to enhance efficiency of cancer chemotherapy. We analysed programmed cell death pathways of v-myb-transformed BM2 monoblasts induced by arsenic trioxide, cycloheximide and camptothecin with U937 promonocytes as a reference cell line. We show that induced death of BM2 cells is not executed by caspases but rather by alternative cell death pathways. Camptothecin induces the lysosome-dependent cell death, arsenic trioxide induces autophagy, and most of cycloheximide-treated BM2 cells die by necrosis. The fact that alternative cell death pathways can be switched in cells with defects in activation and/or function of caspases suggests that understanding and targeting of these pathways could improve therapy of cancer cells suffering from defective apoptosis.