| First Author | Saxena A | Year | 2014 |
| Journal | Cancer Lett | Volume | 355 |
| Issue | 1 | Pages | 141-7 |
| PubMed ID | 25218594 | Mgi Jnum | J:216990 |
| Mgi Id | MGI:5610111 | Doi | 10.1016/j.canlet.2014.09.006 |
| Citation | Saxena A, et al. (2014) Aldose reductase inhibition suppresses azoxymethane-induced colonic premalignant lesions in C57BL/KsJ-db/db mice. Cancer Lett 355(1):141-7 |
| abstractText | 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-beta2, AKT, COX-2 and iNOS in the colonic mucosa of AOM-treated mice were significantly decreased by fidarestat. The serum levels of IL-1alpha, IP-10, MIG, TNF-alpha and VEGF are significantly suppressed in AOM + fidarestat treated obese mice. Fidarestat also decreased the expression of COX-2, iNOS, XIAP, survivin, beta-catenin and NF-kappaB 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. |
