Use of defatted flaxseed meal reduces precancerous colon lesions in C57BL/6 mice 1

PURPOSE: To investigate the hemopreventive effect of defatted flaxseed meal in C57BL/6 mice after induction of precancerous colon lesions with 1.2-dimethylhydrazine (DMH). METHODS: Thirty-six 12-week-old C57BL/6 mice were divided into three treatment groups(nof 12 in each group): (1) diet with 10% defatted flaxseed meal; (2) diet with defatted flaxseed meal and precancerous colon lesions induced by DMH; and (3) precancerous colon lesions induced by DMH, without defatted flaxseed meal. The incidence of aberrant crypt foci (ACF), oxidative processes, expression of tumor suppressor proteins and cyclins, as well as the profile of short-chain fatty acids (SCFA) in animal feces were investigated in the presence and absence of DMH. RESULTS: The rats consuming defatted flaxseed meals showed lesions with lower multiplicity and a reduced incidence of lesions. No changes in the expression of tumor suppressor proteins and those involved in cell cycle control were detected. CONCLUSION: Defatted flaxseed meal protected the distal colon of mice from precancerous lesions. (Authors abstract)

Among the different types of cancer, colorectal cancer (CRC) is the third most common type worldwide in both sexes. CRC is characterized by uncontrolled growth of malignant cells arising from a series of genetic errors that accumulate over the years, which have invasive potential and may spread to other regions. Flaxseed provides as much as 75–800 times the amount of lignans compared to other oil seeds, cereals, legumes, fruits and vegetables. It is also a particularly rich source of the lignan secoisolariciresinol diglycoside (SDG).  SDG is a plant lignan that is converted into mammalian lignans by bacteria in the colon of humans and other animals. They are biologically active phytochemicals with apparent anticancer and antioxidant potential. When consumed, SDG is converted by intestinal microflora into two lignan metabolites, enterodiol and enterolactone. Lignan metabolites act as antioxidants and free radical scavengers, which may decrease the risk of carcinogenesis, protecting the cell from free radicals and DNA damage. In general, mutations in tumorigenesis may cause activation of oncogenes, inactivation of tumor suppressor genes and alterations in DNA repair genes. The proteins p16, p21 and p53 are inhibitors of the cyclin-dependent kinase (CDK), besides cyclin D1, which is responsible for the phosphorylation of the pRB repressor protein, leading to cell cycle arrest in G115.

The purpose of this investigation was to evaluate the chemopreventive effect of defatted flaxseed meal in C57BL/6 mice after the induction of precancerous colon lesions with DMH. The effects of this meal on the incidence of ACF, oxidative processes and expression of the tumor suppressor proteins p53, p16 and p21, as well as cyclins (D and E), were determined. The profile of the short-chain fatty acids (SCFA) acetate, propionate and butyrate in animal feces in the presence and absence of DMH were examined.
The results showed that defatted flaxseed meals could protect animals from precancerous colon lesions. The highest number of ACF induced by DMH and the protective effect of the meal was evident in the distal colon. The higher number of lesions in the distal portion of the colon in rodents treated with DMH has been reported in other studies. DMH induces proliferation of colon tumors, especially in the rectum and sigmoid portion, which may also occur around the duodenum-jejunum junction. The mechanism of action of this drug probably involves the disruption of the DNA methylation mediated by cytochrome P45025. Given the results, it is necessary to clarify how the flaxseed meal could exert protective effects.
In the present study, an attempt was made to relate the defatted flaxseed meal effects with the increased expression of the tumor suppressor proteins p53, p21 and p16 and a decreased expression of proteins involved in cell cycle control, cyclin E and cyclin D1.  Defatted flaxseed meal in DMH-treated animals did not affect the expression of these proteins. The consumption of defatted flax flour did not increase the concentration of fecal SCFA,  results not consistent with those in the literature since it was not possible to determine whether the SCFAs protected the colon from an increased incidence of ACF.  Taken together, the findings suggest that more studies need to be performed to try to elucidate the mechanisms, focusing on the relationship between fiber intake and the modulation of gut microbiota. In this study, none of the tests showed a potential beneficial effect against pre-cancerous lesions. Nevertheless, the defatted flaxseed was able to protect the development of lesion in the distal colon of mice. (Editors comments)