Dietary fish oil and pectin enhance colonocyte apoptosis in part through suppression of PPARdelta/PGE2 and elevation of PGE3.
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.
Vanamala
J
J
Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
Glagolenko
A
A
Yang
P
P
Carroll
R J
RJ
Murphy
M E
ME
Newman
R A
RA
Ford
J R
JR
Braby
L A
LA
Chapkin
R S
RS
Turner
N D
ND
Lupton
J R
JR
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003106:Colon / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D003110:Colonic Neoplasms / Q000517:prevention & control*; D004041:Dietary Fats; D015232:Dinoprostone / Q000037:antagonists & inhibitors*; D005395:Fish Oils / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D008297:Male; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control; D047494:PPAR delta / Q000037:antagonists & inhibitors*; D010368:Pectins / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004041:Dietary Fats; D005395:Fish Oils; D047494:PPAR delta; C033246:prostaglandin E3; D010368:Pectins; D000527:Alprostadil; D015232:Dinoprostone