Aldose reductase inhibition suppresses azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice

Ashish Saxena, Mohammad Shoeb, Ravinder Tammali, Kota Ramana, Satish Srivastava

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Type-2 diabetes and obesity-related metabolic abnormalities are major risk factors for the development of colon cancer. In the present study, we examined the effects of polyol pathway enzyme aldose reductase (AR) inhibitor, fidarestat, on the development of azoxymethane (AOM)-induced colonic premalignant lesions in C57BL/KsJ-db/db obese mice. Our results indicate that fidarestat given in the drinking water caused a significant reduction in the total number of colonic premalignant lesions in the AOM treated obese mice. Further, the expression levels of PKC-β2, AKT, COX-2 and iNOS in the colonic mucosa of AOM-treated mice were significantly decreased by fidarestat. The serum levels of IL-1α, IP-10, MIG, TNF-α and VEGF are significantly suppressed in AOM-+-fidarestat treated obese mice. Fidarestat also decreased the expression of COX-2, iNOS, XIAP, survivin, β-catenin and NF-. κB in high glucose-treated HT29 colon cancer cells. In conclusion, our results indicate that fidarestat inhibits the development of colonic premalignant lesions in an obesity-related colon cancer and is chemopreventive to colorectal carcinogenesis in obese individuals.

Original languageEnglish (US)
Pages (from-to)141-147
Number of pages7
JournalCancer Letters
Volume355
Issue number1
DOIs
StatePublished - Dec 1 2014

Fingerprint

Azoxymethane
Aldehyde Reductase
Obese Mice
Colonic Neoplasms
Obesity
Catenins
Interleukin-1
Drinking Water
Type 2 Diabetes Mellitus
Vascular Endothelial Growth Factor A
fidarestat
Carcinogenesis
Mucous Membrane
Glucose
Enzymes
Serum

Keywords

  • Aldose reductase
  • Colon cancer
  • Obesity
  • Oxidative stress and inflammation

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Aldose reductase inhibition suppresses azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice. / Saxena, Ashish; Shoeb, Mohammad; Tammali, Ravinder; Ramana, Kota; Srivastava, Satish.

In: Cancer Letters, Vol. 355, No. 1, 01.12.2014, p. 141-147.

Research output: Contribution to journalArticle

Saxena, Ashish ; Shoeb, Mohammad ; Tammali, Ravinder ; Ramana, Kota ; Srivastava, Satish. / Aldose reductase inhibition suppresses azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice. In: Cancer Letters. 2014 ; Vol. 355, No. 1. pp. 141-147.
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