title: 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 receptor γ (PPAR γ ) 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), PPAR γ , and β -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 PPAR γ were 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 of β -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 PPAR γ in 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.
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh 160014, India.
authors.forename: Shevali
authors.initials: S
authors.lastname: Kansal
authors.affiliation: Department of Histopathology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012, India.
authors.forename: Kim
authors.initials: K
authors.lastname: Vaiphei
authors.affiliation: Department of Biochemistry, Panjab University, Chandigarh 160014, India.
authors.forename: Navneet
authors.identifier: 0000-0001-6063-3473
authors.initials: N
authors.lastname: Agnihotri
mesh_terms: D000818:Animals; D002518:Ceramides / Q000096:biosynthesis; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004127:Dimethylhydrazines / Q000633:toxicity; D005395:Fish Oils / Q000008:administration & dosage*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D047495:PPAR gamma / Q000096:biosynthesis; D051381:Rats; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000096:biosynthesis
chemical_list: D002518:Ceramides; D004127:Dimethylhydrazines; D005395:Fish Oils; D047495:PPAR gamma; D051176:beta Catenin; D051546:Cyclooxygenase 2