Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARdelta/PGE2 and elevation of PGE3. Academic Article uri icon


  • 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 E(2) (PGE(2)), PGE(3), microsomal prostaglandin E synthase-2 (mPGES-2), total beta-catenin, nuclear beta-catenin staining (%) and peroxisome proliferator-activated receptor delta (PPARdelta) 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 PGE(2)) and the Wnt/beta-catenin pathway [total beta-catenin and nuclear beta-catenin staining (%); P < 0.01] compared with the CC diet. Downregulation of COX and Wnt/beta-catenin pathways was associated with a concurrent suppression (P < 0.05) of PPARdelta levels in FP-fed rats. In addition, colonic mucosa from FP animals contained (P < 0.05) a proapoptotic, eicosapentaenoic acid-derived COX metabolite, PGE(3). These results indicate that FP enhances colonocyte apoptosis in AOM-alone and irradiated AOM rats, in part through the suppression of PPARdelta and PGE(2) and elevation of PGE(3). 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.

published proceedings

  • Carcinogenesis

altmetric score

  • 3

author list (cited authors)

  • Vanamala, J., Glagolenko, A., Yang, P., Carroll, R. J., Murphy, M. E., Newman, R. A., ... Lupton, J. R.

citation count

  • 88

complete list of authors

  • Vanamala, J||Glagolenko, A||Yang, P||Carroll, RJ||Murphy, ME||Newman, RA||Ford, JR||Braby, LA||Chapkin, RS||Turner, ND||Lupton, JR

publication date

  • April 2008