Interaction of polyunsaturated fatty acids and sodium butyrate during apoptosis in HT-29 human colon adenocarcinoma cells
Language English Country Germany Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- Adenocarcinoma metabolism MeSH
- Apoptosis * drug effects MeSH
- Cell Cycle drug effects MeSH
- HT29 Cells MeSH
- Butyrates metabolism MeSH
- Microscopy, Fluorescence MeSH
- Caspase 3 MeSH
- Caspase 9 MeSH
- Caspases drug effects metabolism MeSH
- Arachidonic Acid administration & dosage MeSH
- Docosahexaenoic Acids administration & dosage MeSH
- Humans MeSH
- Membrane Potentials drug effects MeSH
- Colonic Neoplasms metabolism MeSH
- Fatty Acids, Unsaturated metabolism MeSH
- Lipid Peroxidation drug effects MeSH
- Poly(ADP-ribose) Polymerases drug effects metabolism MeSH
- Proto-Oncogene Proteins drug effects metabolism MeSH
- Flow Cytometry MeSH
- Reactive Oxygen Species metabolism MeSH
- Dose-Response Relationship, Drug MeSH
- Blotting, Western MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Butyrates MeSH
- CASP3 protein, human MeSH Browser
- CASP9 protein, human MeSH Browser
- Caspase 3 MeSH
- Caspase 9 MeSH
- Caspases MeSH
- Arachidonic Acid MeSH
- Docosahexaenoic Acids MeSH
- Fatty Acids, Unsaturated MeSH
- Poly(ADP-ribose) Polymerases MeSH
- Proto-Oncogene Proteins MeSH
- Reactive Oxygen Species MeSH
BACKGROUND: Dysregulation of the balance between cell growth and death in the colonic epithelium is associated with cancer promotion. Understanding how cell death in this self-renewing tissue is regulated and how it is influenced by interaction of specific dietary components, especially fat and fibre, could lead to improved treatment and prevention strategies for cancer. AIM OF THE STUDY: The effects of two types of polyunsaturated fatty acids (PUFAs)--arachidonic (AA, 20:4, n-6) or docosahexaenoic (DHA, 22:6, n-3)--on the response of human colon adenocarcinoma HT-29 cells to sodium butyrate (NaBt) were investigated. METHODS: The parameters reflecting cell proliferation and cell death were studied together with oxidative response, mitochondrial membrane potential (MMP) and changes of selected regulatory molecules associated with cell cycle (p27(Kip1) and p21(Cip1/WAF1)) and apoptosis (caspase-3, caspase-9, poly (ADP-ribose) polymerase--PARP, Bcl-2, Bax, Bak,Mcl-1). RESULTS: We demonstrated that pre-treatment with either AA or DHA attenuated cell cycle arrest caused by NaBt which is associated with modulation of p27(Kip1), but not p21(Cip1/WAF1) protein expression. On the other hand, PUFAs sensitised HT-29 cells to NaBt-induced apoptosis. An increased amount of floating cells and cells in the subG(0)/G(1) population was associated with increased reactive oxygen species production, lipid peroxidation, decrease of MMP, activation of caspase-3 and -9, PARP cleavage, and decrease in the expression of antiapoptotic Mcl-1 protein. The observed effects were modulated by the addition of a protein synthesis inhibitor, cycloheximide, and partially reversed by the antioxidant Trolox. CONCLUSIONS: PUFAs may have beneficial effects in the colon enhancing apoptosis induced by NaBt. Alteration of cell membrane lipid composition and potentiation of oxidative processes accompanied by changes in mitochondria followed by stimulation of apoptotic cascade components play a role in these effects.
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