Effect of Different Amount of Dietary n-3 PUFA on Colon Carcinogenesis in DMH-treated Rats.
- Author:
Hyun Suh PARK
1
;
Hye Kyoung KWAK
;
Min Seok KIM
Author Information
1. Department of Food & Nutrition, Kyung Hee University, Seoul, Korea. hspark@khu.ac.kr
- Publication Type:Original Article
- Keywords:
n-3 PUFA;
cell proliferation;
apoptosis;
COX-2;
Bax;
Bcl-2;
eicosanoid
- MeSH:
Animals;
Apoptosis;
Blotting, Western;
Body Weight;
Carcinogenesis*;
Cell Proliferation;
Colon*;
Control Groups;
Diet;
Dimenhydrinate;
Dinoprostone;
Eicosanoids;
Fatty Acids, Omega-3*;
Genes, bcl-2;
Humans;
Male;
Mucous Membrane;
Rats*;
Rats, Sprague-Dawley;
RNA, Messenger
- From:The Korean Journal of Nutrition
2005;38(10):807-816
- CountryRepublic of Korea
- Language:Korean
-
Abstract:
The objective of the study was to observe the effect of n-3 PUFA on cell proliferation and apoptosis by determining mRNA and protein of COX-2 and eicosanoid product and the mRNA and protein of Bu and Bcl-2 related to apoptosis in colon carcinogenesis of 1,2- dimethylhydrazine (DMH)-treated rats. Ninety male Sprague Dawley rats weighing about 170g were divided into 3 groups, control and n-3 PUFA supplemented groups (FO group: 6.2 mmoles n-3 PUFA; 2FO group: 12.4 mmoles n-3 PUFA) and fed experimental diet for 14 weeks. All rats were intramuscularly injected with DMH 15 mg/kg twice a week for 6 weeks to deliver total dose of 180 mg/kg body weight. Compared with the control group, 6.2 mmoles n-3 PUFA significantly reduced the levels of mRNA and protein expression of COX-2 and 2-series eicosanoids (TXB2 and PGE2 and decreased cell proliferation in colonic mucosa. However, high levels of n-3 PUFA supplementation significantly increased the levels of mRNA and protein expression of COX-2, TXB2 and PGE2. and increased cell proliferation which was similar level to that of control group. Compared with the control group, n-3 PUFA, regardless of the amount, significantly increased apoptotic index in colonic mucosa. Western blot and RT-PCR analyses showed that the levels of mRNA and protein expression of Bax were significantly increased by 6.2 mmoles n-3 PUFA, but decreased by 12.4 mmoles n-3 PUFA. The analyses also showed the levels of mRNA and protein expression of Bcl-2 were significantly reduced by 6.2 mmoles n-3 PUFA, but increased by 12.4 mmoles n-3 PUFA. The ratio of Bcl-2/Bax in mRNA and protein was significantly reduced by 6.2 mmoles n-3 PUFA but increased by 12.4 mmoles n-3 PUFA. Overall, these results indicate that n-3 PUFA could be effective in preventing colon carcinogenesis by reducing cell proliferation with lower level of COX-2 and 2-series eicosanoid, and increasing apoptosis by inducing pro-apoptotic gene, Bax and inhibiting anti-apoptotic gene, Bcl-2 in the colonic mucosa of DMH-treated rats. However, high level of n-3 PUFA supplementation could stimulate colon carcinogenesis by increasing cell proliferation and inhibiting apoptosis.
