Fish oil enhances targeted apoptosis during colon tumor initiation in part by downregulating Bcl-2.

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.