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Carcinogenesis Advance Access originally published online on November 16, 2007
Carcinogenesis 2008 29(4):790-796; 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. Vanamala, A. Glagolenko1, P. Yang3, R.J. Carroll2, M.E. Murphy2, R.A. Newman3, J.R. Ford1, L.A. Braby1, R.S. Chapkin, N.D. Turner and J.R. Lupton*

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

* To whom correspondence should be addressed. Tel: 979-845-0850; Fax: 979-862-1862; Email: jlupton{at}ag.tamu.edu

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 {delta} (PPAR{delta}) 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 PPAR{delta} 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 PPAR{delta} 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.

Abbreviations: AA, arachidonic acid; AOM, azoxymethane; CC, corn oil and cellulose; DHA, docosahexanoic acid; EPA, eicosapentaenoic acid; 12-HETE, 12-hydroxy-eicosatetraenoic acid; 13-HODE, 13-hydroxy-octadecadienoic acid; LA, linoleic acid; LC/MS/MS, Liquid chromatography/tandem mass spectrometry; LOX, lipoxygenase; mPGES-2, microsomal prostaglandin E synthase-2; PBS, phosphate-buffered saline; PG, prostaglandin; PGE2, prostaglandin E2; PPAR{delta}, peroxisome proliferator-activated receptor {delta}; PUFA, polyunsaturated fatty acid

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


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