Platelets are implicated in the pathogenesis of various
chronic diseases including
cancer. The main objective of the present study was to determine if dietary
fish oil and
piroxicam, known modulators of colon
tumorigenesis, effect
transforming growth factor (TGF)-betas and
cyclooxygenase (COX)
isozymes in the platelets of colon
tumor-bearing male F344 rats. TGF-betas and COXs are important in the development of
chronic illnesses including
colon cancer. Animals harboring preneoplastic colonic lesions were randomly allocated to a
low fat diet (5% by weight--low
corn oil, LFC) and three high fat diets (23% by weight--high
corn oil, HFC; high
corn oil containing 150-ppm
piroxicam, HFC+P; and high
fish oil, HFF) for 16 weeks.
TGF-beta1,
TGF-beta2, COX-1 and COX-2
protein levels were assessed in the platelets by Western blot analysis. Active
TGF-beta1 (12.5 kDa) level was significantly lower in the platelets of the HFC+P group (p < 0.001), whereas precursor
TGF-beta1 (39 kDa) level was significantly lower in the platelets of the HFF group (p < 0.001). The anti-rabbit
TGF-beta2 polyclonal antibody did not detect the 13-kDa active
TGF-beta2 protein in the platelets. However a 29-kDa
protein, potentially a precursor of
TGF-beta2, was detected in the platelets of all the groups and was significantly lower in the HFC+P and HFF groups than in LFC and HFC (p < 0.001). COX-1 level was significantly lower in the HFF group than the other three groups (p < 0.001). COX-2
protein was detected in the platelets of all diet groups.
Piroxicam in the presence of high
corn oil (HFC+P) significantly lowered the level of COX-2 (p < 0.001), without having any effect on COX-1 level. These findings conclusively show that LFC and HFC differ from HFF and HFC+P, and
piroxicam differs from
fish oil, in regulating the levels of TGF-betas and COX in the platelets. This supports the conjecture that the levels of bioactive constituents of the platelets are profoundly modulated by dietary
lipids, which in turn could influence the pathogenesis of
chronic illnesses.