Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARδ/PGE2 and elevation of PGE3

J. Vanamala, A. Glagolenko, P. Yang, R. J. Carroll, M. E. Murphy, R. A. Newman, J. R. Ford, L. A. Braby, R. S. Chapkin, N. D. Turner, J. R. Lupton

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

We have shown that dietary fish oil and pectin (FP) protects against radiation-enhanced colon cancer by upregulating apoptosis in colonic mucosa. To investigate the mechanism of action, we provided rats (n = 40) with diets containing the combination of FP or corn oil and cellulose (CC) prior to exposure to 1 Gy, 1 GeV/nucleon Fe-ion. All rats were injected with a colon-specific carcinogen, azoxymethane (AOM; 15 mg/kg), 10 and 17 days after irradiation. Levels of colonocyte apoptosis, prostaglandin E2 (PGE2), PGE3, microsomal prostaglandin E synthase-2 (mPGES-2), total β-catenin, nuclear β-catenin staining (%) and peroxisome proliferator-activated receptor δ (PPARδ) expression were quantified 31 weeks after the last AOM injection. FP induced a higher (P < 0.01) apoptotic index in both treatment groups, which was associated with suppression (P < 0.05) of antiapoptotic mediators in the cyclooxygenase (COX) pathway (mPGES-2 and PGE2) and the Wnt/β-catenin pathway [total β-catenin and nuclear β-catenin staining (%); P < 0.01] compared with the CC diet. Downregulation of COX and Wnt/β-catenin pathways was associated with a concurrent suppression (P < 0.05) of PPARδ levels in FP-fed rats. In addition, colonic mucosa from FP animals contained (P < 0.05) a proapoptotic, eicosapentaenoic acid-derived COX metabolite, PGE3. These results indicate that FP enhances colonocyte apoptosis in AOM-alone and irradiated AOM rats, in part through the suppression of PPARδ and PGE2 and elevation of PGE3. These data suggest that the dietary FP combination may be used as a possible countermeasure to colon carcinogenesis, as apoptosis is enhanced even when colonocytes are exposed to radiation and/or an alkylating agent.

Original languageEnglish (US)
Pages (from-to)790-796
Number of pages7
JournalCarcinogenesis
Volume29
Issue number4
DOIs
StatePublished - Apr 2008

All Science Journal Classification (ASJC) codes

  • Cancer Research

Fingerprint Dive into the research topics of 'Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARδ/PGE<sub>2</sub> and elevation of PGE<sub>3</sub>'. Together they form a unique fingerprint.

Cite this