Interaction of polyunsaturated fatty acids and sodium butyrate during apoptosis in HT-29 human colon adenocarcinoma cells
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- Hofmanová, J., Vaculová, A., Lojek, A. et al. Eur J Nutr (2005) 44: 40. doi:10.1007/s00394-004-0490-2
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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.
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 (p27Kip1 and p21Cip1/WAF1) and apoptosis (caspase-3, caspase-9, poly (ADP-ribose) polymerase – PARP, Bcl-2, Bax, Bak,Mcl-1).
We demonstrated that pre-treatment with either AA or DHA attenuated cell cycle arrest caused by NaBt which is associated with modulation of p27Kip1, but not p21Cip1/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 subG0/G1 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.
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.
Key wordscolon cancerdietpolyunsaturated fatty acidsbutyrateapoptosis
foetal calf serum
mitochondrial membrane potential
polyunsaturated fatty acids
reactive oxygen species
thiobarbituric acid reactive substances