Secoisolariciresinol diglucoside rich extract of L. usitatissimum prevents diabetic colon cancer through inhibition of CDK4

Biomed Pharmacother. 2016 Oct:83:733-739. doi: 10.1016/j.biopha.2016.07.041. Epub 2016 Jul 29.

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.

Keywords: CDK4; Colon cancer associated with type 2 diabetes mellitus; DMH; L. usitatissimum; Secoisolariciresinol diglucoside.

MeSH terms

  • Animals
  • Biomarkers, Tumor / metabolism
  • Butylene Glycols / pharmacology
  • Butylene Glycols / therapeutic use*
  • Cell Proliferation / drug effects
  • Colonic Neoplasms / drug therapy*
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / pathology
  • Colonic Neoplasms / prevention & control*
  • Cyclin-Dependent Kinase 4 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 4 / genetics
  • Cyclin-Dependent Kinase 4 / metabolism
  • Cytokines / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / enzymology
  • Diabetes Mellitus, Type 2 / genetics
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Flax / chemistry*
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glucose Tolerance Test
  • Glucosides / pharmacology
  • Glucosides / therapeutic use*
  • Hyperglycemia / complications
  • Hyperglycemia / drug therapy
  • Hyperglycemia / pathology
  • Inflammation Mediators / metabolism
  • Male
  • Phytochemicals / analysis
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Proliferating Cell Nuclear Antigen / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley

Substances

  • Biomarkers, Tumor
  • Butylene Glycols
  • Cytokines
  • Glucosides
  • Inflammation Mediators
  • Phytochemicals
  • Plant Extracts
  • Proliferating Cell Nuclear Antigen
  • RNA, Messenger
  • Cdk4 protein, rat
  • Cyclin-Dependent Kinase 4
  • secoisolariciresinol diglucoside