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Fish oil enhances targeted apoptosis during colon tumor initiation in part by downregulating Bcl-2
Mee Young Hong1, Robert S Chapkin, Laurie A Davidson
1Faculty of Nutrition, Texas A&M University, College Station, TX 77843, USA.
Abstract:
We have shown that fish oil is protective against colon tumorigenesis, primarily by upregulating apoptosis. Production of prostaglandin E2 (PGE2) in colon cancer cells by cyclooxygenase (COX)-I and -II is known to inhibit apoptosis by induction of bcl-2. Because we have shown that fish oil downregulates PGE2 and COX-II, we hypothesized that this upregulation of apoptosis would be coincident with a downregulation of bcl-2. Bcl-2 was localized within the colonic crypt by quantitative immunohistochemistry (IHC), and scraped colonic mucosa was used for immunoblot analysis of bcl-2. The tissue used for bcl-2 analysis was from the rats used to determine apoptosis. Briefly, tissues were collected from rats consuming diets containing either corn oil or fish oil at 3, 6, 9, and 12 h after carcinogen injection. The correlation between bcl-2 and apoptosis was also determined. Bcl-2 expression decreased until 9 h (P < 0.05), whereas apoptosis increased until 9 h (P < 0.01). Bcl-2 expression and apoptosis were negatively correlated in both the proximal (P < 0.05) and distal colon (P < 0.005). Fish oil decreased bcl-2 expression (P < 0.05) and increased apoptosis (P < 0.05) in the top third of the crypt in the distal colon. In conclusion, one pathway by which fish oil may mediate apoptosis and thus protect against colon tumorigenesis is by downregulation of anti-apoptotic bcl-2.
Insights
Fish oil protects against colon cancer by increasing apoptosis, a programmed cell death. This effect is linked to fish oil
Area of Science:
- Oncology
- Molecular Biology
- Nutrition Science
Background:
- Colon cancer is a significant health concern.
- Fish oil has demonstrated protective effects against colon tumorigenesis.
- Prostaglandin E2 (PGE2) and cyclooxygenase (COX)-II are implicated in inhibiting apoptosis via bcl-2 induction in colon cancer cells.
Purpose of the Study:
- To investigate the hypothesis that fish oil's upregulation of apoptosis is associated with a downregulation of bcl-2.
- To determine the correlation between bcl-2 expression and apoptosis in the colon.
- To elucidate the mechanism by which fish oil exerts its protective effects against colon tumorigenesis.
Main Methods:
- Quantitative immunohistochemistry (IHC) was used to localize bcl-2 within the colonic crypt.
- Immunoblot analysis of bcl-2 was performed on scraped colonic mucosa.
- Tissues were collected from rats fed corn oil or fish oil diets at various time points post-carcinogen injection.
Main Results:
- Bcl-2 expression decreased while apoptosis increased until 9 hours post-injection, showing a negative correlation.
- Fish oil consumption significantly decreased bcl-2 expression (P < 0.05).
- Fish oil consumption significantly increased apoptosis (P < 0.05) in the distal colon.
Conclusions:
- Fish oil downregulates anti-apoptotic bcl-2 expression.
- This downregulation of bcl-2 by fish oil is a key pathway mediating increased apoptosis.
- Fish oil's ability to upregulate apoptosis by downregulating bcl-2 contributes to its protective role in colon tumorigenesis.
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