In addition to its ability to act as a promising inducer of tumor-specific cell death, TRAIL has also been shown to stimulate signaling pathways leading to cancer cell survival. We examined the changes of anti-apoptotic Mcl-1 protein level following TRAIL treatment of human cell lines representing different stages of colon carcinogenesis-adenocarcinoma (HT-29, HCT116) or secondary metastasis (SW620), together with cell line derived from human fetal colon (FHC). While TRAIL was capable of triggering an anti-apoptotic signaling leading to significant early ERK-mediated transcriptional up-regulation of Mcl-1 in selected colon adenocarcinoma cell lines, none or very limited effects were demonstrated in cell lines derived from colon lymph node metastasis or fetal colon, respectively. We demonstrated an immediate impact of Mcl-1 protein level manipulations on the course of early acute apoptotic response of colon adenocarcinoma cells to TRAIL. It is therefore essential to consider the dynamics of modulation of Mcl-1 level and the balance between TRAIL-induced pro- and anti-apoptotic pathways when predicting the response of cells in different stages of cancer development, and designing the anticancer therapy using TRAIL.
- MeSH
- epitelové buňky metabolismus MeSH
- lidé MeSH
- metastázy nádorů patologie MeSH
- nádorové buněčné linie MeSH
- nádory tračníku metabolismus patologie MeSH
- protein TRAIL fyziologie MeSH
- protoonkogenní proteiny c-bcl-2 genetika MeSH
- regulace genové exprese MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
The resistance of some cancer cells to TRAIL-induced apoptosis is a major obstacle in successful clinical application of this cytokine. Combination treatment with agents capable of sensitising the cells to TRAIL effects is beneficial for new cancer treatment strategies. Docosahexaenoic acid (DHA) is under intense investigation for its ability to affect cancer cell growth and apoptosis. We demonstrated a modulation of TRAIL-induced apoptosis of HT-29 human colon cancer cells by DHA on the molecular (pro-caspase-3, -8, Bid, PARP cleavage) and cellular (cell viability and adhesion) level. To conclude, TRAIL and DHA were shown to cooperate in the induction of colon cancer cell apoptosis.
- MeSH
- adenokarcinom patologie MeSH
- apoptóza genetika MeSH
- buněčná adheze MeSH
- financování organizované MeSH
- kyseliny dokosahexaenové farmakologie MeSH
- lékové interakce MeSH
- lidé MeSH
- membránové glykoproteiny fyziologie MeSH
- nádorové buňky kultivované MeSH
- nádory tračníku patologie MeSH
- proteiny regulující apoptózu MeSH
- regulace genové exprese u nádorů účinky léků MeSH
- TNF-alfa fyziologie MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- MeSH
- apoptóza genetika účinky záření MeSH
- ethanol farmakologie MeSH
- lidé MeSH
- membránové glykoproteiny fyziologie MeSH
- nádorové proteiny metabolismus MeSH
- nádory tračníku enzymologie metabolismus patologie MeSH
- transportní proteiny metabolismus MeSH
- tumor nekrotizující faktory fyziologie MeSH
- Check Tag
- lidé MeSH
