DHA-mediated enhancement of TRAIL-induced apoptosis in colon cancer cells is associated with engagement of mitochondria and specific alterations in sphingolipid metabolism
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24953781
DOI
10.1016/j.bbalip.2014.06.005
PII: S1388-1981(14)00116-4
Knihovny.cz E-zdroje
- Klíčová slova
- Apoptosis, Colon cancer, Docosahexaenoic acid, Lipid metabolism, TRAIL,
- MeSH
- adenokarcinom genetika metabolismus patologie MeSH
- apoptóza účinky léků genetika MeSH
- cytochromy c metabolismus MeSH
- inhibitory apoptózy MeSH
- kinasa eIF-2 genetika metabolismus MeSH
- kyseliny dokosahexaenové farmakologie MeSH
- lidé MeSH
- membránový potenciál mitochondrií účinky léků MeSH
- mitochondrie účinky léků metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory tračníku genetika metabolismus patologie MeSH
- protein Bak genetika metabolismus MeSH
- protein TRAIL farmakologie MeSH
- protein X asociovaný s bcl-2 genetika metabolismus MeSH
- regulace genové exprese u nádorů * MeSH
- sfingolipidy chemie klasifikace metabolismus MeSH
- signální transdukce MeSH
- stres endoplazmatického retikula účinky léků MeSH
- synergismus léků MeSH
- transkripční faktor CHOP genetika metabolismus MeSH
- X-vázaný inhibitor apoptózy genetika metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- BAK1 protein, human MeSH Prohlížeč
- BAX protein, human MeSH Prohlížeč
- cytochromy c MeSH
- DDIT3 protein, human MeSH Prohlížeč
- EIF2AK3 protein, human MeSH Prohlížeč
- inhibitory apoptózy MeSH
- kinasa eIF-2 MeSH
- kyseliny dokosahexaenové MeSH
- protein Bak MeSH
- protein TRAIL MeSH
- protein X asociovaný s bcl-2 MeSH
- sfingolipidy MeSH
- TNFSF10 protein, human MeSH Prohlížeč
- transkripční faktor CHOP MeSH
- X-vázaný inhibitor apoptózy MeSH
- XIAP protein, human MeSH Prohlížeč
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.
Citace poskytuje Crossref.org
Colon Cancer and Perturbations of the Sphingolipid Metabolism
