Key Findings
The risk of colon cancer is about 30% in Type 2 diabetes mellitus (T2DM) patients. Previous studies from this laboratory have shown that SDG from flaxseed exerts chemoprotective role in skin cancer by inhibition of CDK4 and upregulation of p53, both key pathways in the onset of the disease. This study in rats showed that an SDG rich extract (SRE) reduced colon cancer associated with T2DM which may be mediated through inhibition of colonic CDK4. There was a significant increase in serum fasting and mean glucose levels in disease control animals. The SRE treated animals showed significantly reduced the serum fasting and mean glucose levels. They also exhibited better results in oral glucose tolerance testing. In addition, there was a significant increase in glycosylated hemoglobin levels in disease control rats and treatment with SRE significantly decreased glycosylated hemoglobin levels. A significant reduction in IL-1b abd an inhibition in inflammation in SRE treated animals. Animals fed SRE had a reduction in crypt formation and hyperplastic cells which suggests an anti-proliferative and chemopreventive effects. Overall the data suggests that SDG produces the beneficial effects of the SDG rich extract are mediated through inhibition of colonic CDK4.
Abstract
BACKGROUND: There is increased risk of colon cancer in both men and women having diabetes. The objective of the study was to evaluate the role of Secoisolariciresinol diglucoside rich extract (SRE) of L.usissatisimum(flaxseed) in colon cancer associated with type 2 diabetes mellitus. MATERIAL AND METHODS: Diabetes was induced by administering high fat diet with low dose streptozotocin model. After 6 weeks, diabetes was confirmed and 1,2 dimethylhydrazine(25mg/kg, sc) weekly administration was from 6th to 18th weeks. Rats were treated with the SRE(500mg/kg) orally from 6th to 24th week. After 24 weeks, various biochemical and enzymatic parameters were estimated. Animals were sacrificed and colon tissue was separated and subjected to analysis of histopathological, PCNA studies and mRNA expression of CDK4. RESULTS: Disease control rats depicted hyperglycaemia, hyperinsulinaemia, elevated pro-inflammatory cytokines and cancer biomarker levels, and marked presence of proliferating cells. Treatment with SRE controlled hyperglycaemia, hyperinsulinaemia, reduced pro-inflammatory cytokines and cancer biomarker levels, and decreased no. of proliferating cells. We found that disease control rats depicted over expression of CDK4 mRNA levels which were reduced by SRE treatment. CONCLUSIONS: SRE of L. usitatissimum exhibited chemopreventive effect in colon cancer associated with type 2 diabetes mellitus which might be mediated through inhibition of CDK4.
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