Flaxseed (Linum usitatissimum L.) and its Total Non digestible Fraction Influence the Expression of Genes Involved in Azoxymethane-induced Colon Cancer in Rats
Flaxseed (Linum usitatissimum L.) and its Total Non digestible Fraction Influence the Expression of Genes Involved in Azoxymethane-induced Colon Cancer in Rats
Year: 2013
Authors: Hernandez-Salazar, M. Guevara-Gonzalez, R.G. Cruz-Hernandez, A. Guevara-Olvera, L. Bello-Perez, L.A. Castano-Tostado, E. Loarca-Pina, G.
Publication Name: Plant Foods Hum Nutr.
Publication Details: Volume 68; Pages 259-267
Abstract:
The influence of flaxseed (Linum usitatissimum L.) and its total non digestible fraction (TNDF) on the expression of genes involved in azoxymethane (AOM) induced colon cancer in Sprague Dawley rats was analyzed. The dose used in the animal model was two tablespoons of flaxseed per day, which is the dose recommended for humans. Flaxseed significantly decreased the crypt multiplicity (10.50 plus or minus 3.5) compared with the AOM treatment (34.00 plus or minus 11.0), which suggests that flaxseed exhibits a preventive effect against colon cancer. Both treatments (flaxseed and TNDF) influence the overexpression of genes involved in cell cycle arrest and mitochondrial apoptosis: p53, p21, bcl2, bax and caspase3. Flaxseed induced the expression of p53 and p21, whereas TNDF triggered the p21 independent expression of p53. This finding suggests that both of these treatments induced cell cycle arrest. In addition, TNDF induced mitochondrial apoptosis because the TNDF plus AOM group exhibited the expression of caspase3, decreased bcl2 expression and increased bax expression. These results suggest that the expression of the analyzed genes is associated with the presence of dietary antioxidants linked to the cell wall of flaxseed. (Authors abstract)
Aberrant crypt foci (ACF) are used to identify some modulators of colon carcinogenesis in animal models. Because the growth, morphological and molecular features of ACF are considered preneoplastic lesions, the use of ACF provides a quantitative approach for the assessment of the disease process and the underlying cellular and molecular events that are affected by cancer preventive or promoting agents. Flaxseed can inhibit colon carcinogenesis in cell cultures and animal models, and this preventive effect might be attributed to the high level of n3 polyunsaturated fatty acids, dietary fibers, and lignans . However, the evaluation of this effect has not been extensively studied. The objective of this study was to determine the effect of flaxseed and its TNDF on the expression of some genes that are involved in azoxymethane (AOM) induced colon cancer in Sprague Dawley rats.
Cancer is related to overproduction of free radicals due the oxidative stress. Plant cell walls containing significant amounts of phenolic components may be the most likely to protect against cancer. The yield of TNDF from flaxseed was 45.64 percent. Although flaxseed and its TNDF did not significantly decrease the total number of ACF, flaxseed significantly decreased the crypt multiplicity. The crypt multiplicity, particularly four or more crypts per focus, is hypothesized to more closely reflect the colon tumor outcome . Thus, the results suggest that flaxseed is better than its TNDF because it attenuates level of crypt formation, as well as its morphological feature. It has been shown that flaxseed can reduce formation, size and multiplicity of aberrant crypt foci. Flaxseed can reduce the expression of COX2 protein in AOM induced colon tumors. Although flaxseed was the only treatment that significantly decreased the crypt multiplicity, the analysis of the gene expression showed that the suggested dose of flaxseed and its TNDF modulated the expressions of genes involved in cell cycle arrest, proliferation and mitochondrial apoptosis. According to the bioaccessibility results, it can be hypothesized that phenolic compounds might be responsible for the observed gene expression. Lignans are diphenolic compounds found in higher plants and are formed by the coupling of two coniferyl alcohol residues that are present in the plant cell wall . It has been suggested that lignans are the main compounds responsible for the anticancer and antioxidant activities of flaxseed and that flaxseed is an important source of these components, particularly a lignan called secoisolariciresinol diglycoside . Plant lignans are converted by bacteria in the human colon (and the colon of other animals) into the mammalian lignans enterodiol (ED) and enterolactone (EL). It has been reported that a subcutaneous injection of 10 mg/kg of EL three times per week reduces the expression of colo 201 human colon cancer cells in athymic mice. Based on this result, which was obtained through Western blot analyses, the authors suggest that the tumor suppression was induced by apoptosis and decreased cell proliferation. The recommended dose of flaxseed (two tablespoons per day for humans) and its TNDF can induce the expression of genes involved in proliferation, cell cycle arrest, and mitochondrial apoptosis (p53, p21, rb, bax, and caspase3). These changes in gene expression might be influenced by the presence of dietary antioxidants associated with dietary fiber, particularly lignans and phenolic acids (mainly ferulic acid). (Editors comments)
