[Enteral nutrition: drug administration via feeding tube]. / Enterale Ernährung: Medikamentenapplikation über Sonden.

Enteral nutrition support via a feeding tube is a preferred and broadly applied way of artificial nutrition in patients who cannot take up orally an adequate amount of nutrients. These patients often need simultaneous drug therapy as well. Thus, there is a high risk of drug-nutrient interactions. Although enteral nutrition is commonly used there is a lack of awareness and knowledge about the appropriate handling and drug administration via the feeding tube. On the one hand, drug-nutrient interactions can lead to clogging of the tube, on the other hand, the change in bioavailability of the drug can have a direct effect on the therapeutic effort. To optimise safety and efficacy of drug therapy in patients with feeding tubes, some basic rules have been set up.

Tributyrin, a butyrate precursor, impairs growth and induces apoptosis and differentiation in pancreatic cancer cells.

BACKGROUND: The aim of this study was to investigate whether tributyrin, a natural butyrate pro-drug, as well as butyrate itself could affect growth, differentiation and apoptosis in two human pancreatic cancer cell lines in culture. MATERIALS AND METHODS: Proliferation was studied by cell counting using crystal violet staining. Cell differentiation was assessed by measuring the alkaline phosphatase activity and cell death by DAPI nuclear staining. RESULTS: In MiaPaca-2 cells both tributyrin and butyrate reduced growth, with IC50 values of 1.1+/-0.2 mmol/ and 3.6+/-0.7 mmol/L respectively. Both 1 mmol/L tributyrin and 3 mmol/L butyrate induced a similar degree of apoptosis in MiaPaca-2 and Capan-l cells and stimulated differentiation in Capan-l cells equally. CONCLUSION: Our data may provide a rationale for the therapeutic use of peroral tributyrin in patients with pancreatic cancer, because this drug enables plasma concentrations of butyrate which inhibit growth, induce differentiation and cause apoptosis in pancreatic cancer cells.

Butyrate-induced differentiation of Caco-2 cells is mediated by vitamin D receptor.

Butyrate in combination with 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] produces a synergistic effect on cell differentiation of human colon cancer cells (Caco-2). The objective of this study was to confirm the role of the vitamin D receptor (VDR) in butyrate-induced cell differentiation of Caco-2. We studied the effects of the novel VDR antagonist ZK 191732 on butyrate-induced cell differentiation and on p21Waf1/Cip1 expression. Butyrate induced cell differentiation which was further enhanced after addition of 1,25-(OH)2D3. Experiments using ZK 191732 indicate that the synergistic effect of butyrate and 1,25-(OH)2D3 was due to butyrate-induced upregulation of VDR. While butyrate alone increased expression of p21Waf1/Cip1 and combined exposure of butyrate and 1,25-(OH)2D3 resulted in a synergistic amplification, p21Waf1/Cip1 expression did not change from the control level after treatment with butyrate plus ZK 191732. These data further imply that butyrate-induced differentiation and p21Waf1/Cip1 expression of Caco-2 cells occur via upregulation of VDR.

Tributyrin, a stable and rapidly absorbed prodrug of butyric acid, enhances antiproliferative effects of dihydroxycholecalciferol in human colon cancer cells.

Tributyrin, a prodrug of natural butyrate, has been evaluated with an aim to overcome pharmacokinetic drawbacks of natural butyrate as a drug, i.e., its rapid metabolization and inability to achieve pharmacologic concentrations in neoplastic cells. We studied the effects of tributyrin on growth, differentiation and vitamin D receptor expression in Caco-2 cells, a human colon cancer cell line. Tributyrin was more potent in inhibiting growth and inducing cell differentiation than natural butyrate. The effect was further enhanced after addition of physiologic concentrations of dihydroxycholecalciferol [(OH)2D3]. The synergistic effect of tributyrin and (OH)2D3 in Caco-2 cells was due to tributyrin-induced overexpression of the vitamin D receptor, as measured by reverse transcriptase-polymerase chain reaction. Treatment with tributyrin increased binding of (OH)2D3 to its receptor 1.5-fold, without any change in receptor affinity. We conclude that tributyrin may, at least in part, exert its growth-reducing and differentiation-inducing effect in Caco-2 cells by an upregulation of 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 human diet.

1,25-Dihydroxycholecalciferol enhances butyrate-induced p21(Waf1/Cip1) expression.

Butyrate, a short-chain fatty acid produced in the colon, as well as its prodrug tributyrin, reduce proliferation and increase differentiation of colon cancer cells. p21(Waf1/Cip1) and p27(Kip1) are negative regulators of cell cycle and are thought to have a key function in the differentiation of various cell lines. We studied the effects of butyrate on differentiation, VDR expression, as well as on p21(Waf1/Cip1) and p27(Kip1) expression in human colon cancer cells (Caco-2). Butyrate induced cell differentiation, which was further enhanced after addition of 1,25-dihydroxycholecalciferol. Synergistic effect of butyrate and dihydroxycholecalciferol in Caco-2 cells was due to butyrate-induced overexpression of VDR. While butyrate as well as dihydroxycholecalciferol increased p21(Waf1/Cip1) and p27(Kip1) expression, in contrast combined exposure of butyrate and dihydroxycholecalciferol resulted in a synergistic amplification of p21(Waf1/Cip1), but not of p27(Kip1) expression. These data imply that butyrate selectively increases p21(Waf1/Cip1) expression via upregulation of VDR in Caco-2 cells.