Dietary fibres are indigestible
food ingredients that reach the colon and are then fermented by colonic bacteria, resulting mainly in the formation of
short-chain fatty acids (SCFA) such as
acetate,
propionate, and
butyrate. Those SCFA, especially
butyrate, are recognised for their potential to act on secondary
chemoprevention by slowing growth and activating apoptosis in
colon cancer cells. Additionally, SCFA can also act on primary prevention by activation of different
drug metabolising
enzymes. This can reduce the burden of
carcinogens and, therefore, decrease the number of mutations, reducing
cancer risk. Activation of
GSTs by
butyrate has been studied on
mRNA,
protein, and
enzyme activity level by real-time RT-PCR,
cDNA microarrays, Western blotting, or photometrical approaches, respectively.
Butyrate had differential effects in colon cells of different stages of
cancer development. In HT29 tumour cells, e.g.,
mRNA GSTA4, GSTP1, GSTM2, and GSTT2 were induced. In LT97
adenoma cells, GSTM3, GSTT2, and MGST3 were induced, whereas GSTA2, GSTT2, and
catalase (CAT) were elevated in primary colon cells. Colon cells of different stages of
carcinogenesis differed in post-transcriptional regulatory mechanisms because
butyrate increased
protein levels of different GST
isoforms and total GST
enzyme activity in HT29 cells, whereas in LT97 cells, GST
protein levels and activity were slightly reduced. Because
butyrate increased
histone acetylation and phosphorylation of ERK in HT29 cells, inhibition of
histone deacetylases and the influence on MAPK signalling are possible mechanisms of GST activation by
butyrate. Functional consequences of this activation include a reduction of DNA damage caused by
carcinogens like
hydrogen peroxide or
4-hydroxynonenal (HNE) in
butyrate-treated colon cells. Treatment of colon cells with the supernatant from an in vitro fermentation of
inulin increased GST activity and decreased HNE-induced DNA damage in HT29 cells. Additional animal and human studies are needed to define the exact role of dietary fibre and
butyrate in inducing GST activity and reducing the risk of
colon cancer.