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Carcinogenesis Advance Access published online on November 16, 2007
Carcinogenesis, doi:10.1093/carcin/bgm256
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© The Author 2007. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPAR{delta}/PGE2 and elevation of PGE3

J. Vanamala1, A. Glagolenko2, P. Yang3, R.J. Carroll4, M.E. Murphy4, R.A. Newman3, J.R. Ford2, L.A. Braby2, R.S. Chapkin1, N.D. Turner1 and J.R. Lupton1,*

1 Faculty of Nutrition
2 Department of Nuclear Engineering
3 University of Texas M.D. Anderson Cancer Center, Houston, 77030
4 Department of Statistics, Texas A&M University, College Station, 77843

* To whom correspondence should be addressed. 213 Kleberg Building, 2253 TAMU, College Station, TX 77843–2253. E-mail: jlupton{at}ag.tamu.edu

We have shown that dietary fish oil/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/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 d after irradiation. Levels of colonocyte apoptosis, prostaglandin E2 (PGE2), PGE3, microsomal PGE Synthase-2, total ß-catenin, nuclear ß-catenin staining (%), and peroxisome proliferator-activated receptor {delta} (PPAR{delta}) expression were quantified 31 wk 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 anti-apoptotic mediators in the cyclooxygenase (COX) pathway (mPGES-2 and PGE2) and the Wnt/ß-catenin pathway (total ß-catenin and nuclear ß-catenin staining (%); P < 0.01) compared to the CC diet. Down-regulation of COX and Wnt/ß-catenin pathways was associated with a concurrent suppression (P < 0.05) of PPAR{delta} levels in FP fed rats. In addition, colonic mucosa from FP animals contained (P < 0.05) a pro-apoptotic, 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 PPAR{delta} and PGE2 and elevation of PGE3. These data suggest that the dietary fish oil/pectin 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.

Key Words: fish oil • apoptosis • prostaglandin • Wnt/beta-catenin • PPAR delta

Received July 31, 2007; revised October 25, 2007; accepted November 4, 2007.


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