Tributyrin is a triglyceride that is obtained through the formal acylation of the three hydroxy groups of glycerol by butyric acid. Tributyrin has been demonstrated to function as an inhibitor, a protective agent, an apoptosis inducer, a prodrug, and an antineoplastic agent. In comparison to butyrate, tributyrin exhibits superior pharmacokinetics and is well tolerated. As a stable and rapidly absorbed prodrug of butyric acid, tributyrin has been shown to enhance the antiproliferative effects of dihydroxycholecalciferol in human colon cancer cells.
Tributyrin, a prodrug of natural butyrate, has been evaluated with the objective of overcoming the pharmacokinetic limitations of natural butyrate as a pharmaceutical agent. These limitations include its rapid metabolization and its inability to achieve pharmacologic concentrations in neoplastic cells. The objective of this study was to examine the impact of tributyrin on the growth, differentiation, and vitamin D receptor expression of Caco-2 cells, a human colon cancer cell line. Tributyrin demonstrated greater potency in inhibiting growth and inducing cell differentiation than natural butyrate. Furthermore, the effect was augmented following the addition of physiologic concentrations of dihydroxycholecalciferol.
Tributyrin may exert its growth-reducing and differentiation-inducing effect in Caco-2 cells, at least in part, by upregulating the vitamin D receptor. This may provide a useful therapeutic approach in chemoprevention and treatment of colorectal cancer by the two nutrients occurring naturally in the human diet.
In normal colonic mucosa, butyrate serves as a primary energy source, promotes growth of normal colonic epithelial cells in vivo and in vitro, and plays a role in preventing certain types of colitis. In contrast, in a wide variety of neoplastic cells, butyrate acts as a potent antineoplastic agent, inhibiting growth and inducing differentiation, thereby restoring a normal phenotype and function.
Despite its initial promise, butyrate is not currently among the drugs employed in cancer treatment.
Tributyrin is a prodrug of butyrate. It is a neutral triglyceride that is likely to overcome the drawbacks of butyrate as a drug. It has more favorable pharmacokinetics and is well tolerated. Filled into gelatin capsules and administered orally, it resulted in millimolar concentrations of butyrate in plasma and cells.
Tributyrin exerts antiproliferative actions on colon cancer cells more potently than butyrate itself.
Tributyrin was more potent than butyrate in reducing the number of Caco-2 cells in culture.