Alterations in Lipid Mediated Signaling and Wnt/β-Catenin Signaling in DMH Induced Colon Cancer on Supplementation of Fish Oil

Abstract

Ceramide mediates inhibition of cyclooxygenase-2 (COX-2) which catalyzes formation of prostaglandin further activating peroxisome proliferator-activated receptorγ(PPARγ) and Wnt/β-catenin pathway; and hence plays a critical role in cancer. Therefore, in current study, ceramide, COX-2, 15-deoxy prostaglandin J2(15-deoxy PGJ2), PPARγ, andβ-catenin were estimated to evaluate the effect of fish oil on lipid mediated and Wnt/β-catenin signaling in colon carcinoma. Male Wistar rats in Group I received purified diet while Groups II and III received modified diet supplemented with FO : CO(1 : 1) and FO : CO(2.5 : 1), respectively. These were further subdivided into controls receiving ethylenediaminetetraacetic acid and treated groups receiving dimethylhydrazine dihydrochloride (DMH)/week for 4 weeks. Animals sacrificed 48 hours after last injection constituted initiation phase and those sacrificed after 16 weeks constituted postinitiation phase. Decreased ceramide and increased PPARγwere observed in postinitiation phase only. On receiving FO+CO(1 : 1)+DMH and FO+CO(2.5 : 1)+DMH in both phases, ceramide was augmented whereas COX-2, 15-deoxy PGJ2, and nuclear translocation ofβ-catenin were reduced with respect to cancerous animals. Decrease was more significant in postinitiation phase with FO+CO(2.5 : 1)+DMH. Treatment with oils increased PPARγin initiation phase but decreased it in postinitiation phase. Hence, fish oil altered lipid mediated signalling in a dose and time dependent manner so as to inhibit progression of colon cancer.