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@article{1194251,
author = {Skender, Belma and Hofmanová, Jiřina and Slavík, Josef and Jelínková, Iva and Machala, Miroslav and Moyer, Marry Pat and Kozubík, Alois and Hyršlová Vaculová, Alena},
article_location = {AMSTERDAM},
article_number = {9},
doi = {http://dx.doi.org/10.1016/j.bbalip.2014.06.005},
keywords = {Docosahexaenoic acid; TRAIL; Apoptosis; Lipid metabolism; Colon cancer},
language = {eng},
issn = {1388-1981},
journal = {Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids},
title = {DHA-mediated enhancement of TRAIL-induced apoptosis in colon cancer cells is associated with engagement of mitochondria and specific alterations in sphingolipid metabolism.},
url = {https://www.sciencedirect.com/science/article/pii/S1388198114001164?via%3Dihub},
volume = {1841},
year = {2014}
}
TY - JOUR
ID - 1194251
AU - Skender, Belma - Hofmanová, Jiřina - Slavík, Josef - Jelínková, Iva - Machala, Miroslav - Moyer, Marry Pat - Kozubík, Alois - Hyršlová Vaculová, Alena
PY - 2014
TI - DHA-mediated enhancement of TRAIL-induced apoptosis in colon cancer cells is associated with engagement of mitochondria and specific alterations in sphingolipid metabolism.
JF - Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids
VL - 1841
IS - 9
SP - 1308-1317
EP - 1308-1317
PB - ELSEVIER SCIENCE BV
SN - 13881981
KW - Docosahexaenoic acid
KW - TRAIL
KW - Apoptosis
KW - Lipid metabolism
KW - Colon cancer
UR - https://www.sciencedirect.com/science/article/pii/S1388198114001164?via%3Dihub
L2 - https://www.sciencedirect.com/science/article/pii/S1388198114001164?via%3Dihub
N2 - Docosahexaenoic acid (DHA), an n-3 polyunsaturated fatty acid present in fish oil, may exert cytotoxic and/or cytostatic effects on colon cancer cells when applied individually or in combination with some anticancer drugs. Here we demonstrate a selective ability of subtoxic doses of DHA to enhance antiproliferative and apoptotic effects of clinically useful cytokine TRAIL (tumor necrosis factor-related apoptosis inducing ligand) in cancer but not normal human colon cells. DHA-mediated stimulation of TRAIL-induced apoptosis was associated with extensive engagement of mitochondrial pathway (Bax/Bak activation, drop of mitochondrial membrane potential, cytochrome c release), activation of endoplasmic reticulum stress response (CHOP upregulation, changes in PERK level), decrease of cellular inhibitor of apoptosis protein (XIAP, cIAP1) levels and significant changes in sphingolipid metabolism (intracellular levels of ceramides, hexosyl ceramides, sphingomyelines, sphingosines; HPLC/MS/MS). Interestingly, we found significant differences in representation of various classes of ceramides (especially C16:0, C24:1) between the cancer and normal colon cells treated with DHA and TRAIL, and suggested their potential role in the regulation of the cell response to the drug combination. These study outcomes highlight the potential of DHA for a new combination therapy with TRAIL for selective elimination of colon cancer cells via simultaneous targeting of multiple steps in apoptotic pathways.
ER -
SKENDER, Belma, Jiřina HOFMANOVÁ, Josef SLAVÍK, Iva JELÍNKOVÁ, Miroslav MACHALA, Marry Pat MOYER, Alois KOZUBÍK and Alena HYRŠLOVÁ VACULOVÁ. DHA-mediated enhancement of TRAIL-induced apoptosis in colon cancer cells is associated with engagement of mitochondria and specific alterations in sphingolipid metabolism. \textit{Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids}. AMSTERDAM: ELSEVIER SCIENCE BV, 2014, vol.~1841, No~9, p.~1308-1317. ISSN~1388-1981. Available from: https://dx.doi.org/10.1016/j.bbalip.2014.06.005.
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