Natural COX-2 inhibitors and effects on colon cancer cells

Abstract

The cyclooxygenase-2 enzyme (COX-2) is involved in prostaglandin biosynthesis and thus plays a significant role in the process of inflammation. Different types of natural compounds can affect the COX-2 enzymatic activity [1]. In recent years it has also been suggested that COX-2 is involved in cancer development [2]. As many natural compounds are present in the human diet this study has focused on discovery of natural COX-2 inhibitors present in food. A number of human fecal water samples (the aqueous phase of feces) from vegetarians were collected and assessed for effects on COX-2 enzymatic activity and also for effects on protein expression level in human colon cancer cells (HT-29). Of 14 samples analyzed, 13 decreased COX-2 protein levels in the cells (19–63% inhibition) [3]. Most samples also significantly decreased prostaglandin (PGE2) production in HT-29 cells [3]. Solid phase extraction was performed to trace the activity of the fecal water samples. The resulting water fraction was found to be responsible for the inhibitory activity of the samples, suggesting that the active compounds are most likely polar in nature. The chemical content of fecal water was analyzed using chromatographic techniques. Gas chromatography-mass spectrometry was used to study the content of the fecal water, with an emphasis on finding phenolic compounds, whereas nuclear magnetic resonance (NMR) was used to obtain an overview of the total fecal water content. The NMR metabolite profiles of vegetarian fecal water samples were very similar, suggesting that the colonic content of the individuals in the study population were similar in composition. A variety of compounds were identified including several phenolic compounds, amino acids and fatty acids. To the best of our knowledge, the use of NMR as a tool in studying colonic contents represents a new approach that would potentially be very useful in colon cancer research.