Butyrate-Induced Differentiation of Caco-2 Cells Is Mediated by Vitamin D Receptor

Gaschott, Tanja; Werz, Oliver; Steinmeyer, Andreas; Steinhilber, Dieter; Stein, Jürgen M.

doi:10.1006/bbrc.2001.5832

Cited by 48 publications

(46 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These findings complement a number of parallel studies undertaken by other groups, which have established cooperation between 1a,25(OH) 2 D 3 and butyrate compounds, such as sodium butyrate (176)(177)(178)(179)(180)(181) . These compounds are SCFA produced during fermentation by endogenous intestinal bacteria and have the capacity to act as histone deacetylases inhibitors.…”

Section: Epigenetic Resistancesupporting

confidence: 85%

The vitamin D receptor in cancer

2008

View full text Add to dashboard Cite

Over the last 25 years roles have been established for vitamin D receptor (VDR) in influencing cell proliferation and differentiation. For example, murine knock-out approaches have revealed a role for the VDR in controlling mammary gland growth and function. These actions appear widespread, as the enzymes responsible for 1a,25-dihydroxycholecalciferol generation and degradation, and the VDR itself, are all functionally present in a wide range of epithelial and haematopoietic cell types. These findings, combined with epidemiological and functional data, support the concept that local, autocrine and paracrine VDR signalling exerts control over cell-fate decisions in multiple cell types. Furthermore, the recent identification of bile acid lithocholic acid as a VDR ligand underscores the environmental sensing role for the VDR. In vitro and in vivo dissection of VDR signalling in cancers (e.g. breast, prostate and colon) supports a role for targeting the VDR in either chemoprevention or chemotherapy settings. As with other potential therapeutics, it has become clear that cancer cells display de novo and acquired genetic and epigenetic mechanisms of resistance to these actions. Consequently, a range of experimental and clinical options are being developed to bring about more targeted actions, overcome resistance and enhance the efficacy of VDR-centred therapeutics. The cancer burdenThe impact of cancer continues to be one of the greatest burdens in the developed world and is also increasingly impacting on the developing world. Approximately 1 . 5 million individuals will die from breast, colon or prostate cancer this year, and the total number of deaths from cancer accounts for 13 % of all deaths worldwide and for one in every four deaths in the UK and USA (1) . The impact is also economic; $280 · 10 9 is spent annually worldwide on the treatment of patients. Many cancers are however preventable, and through lifestyle choices such as smoking, diet and exercise the worldwide incidence of cancer could be cut by 40 % (2,3) . Major risk factors for cancer DietRecently, the appreciation of the impact of diet on cancer has come to the fore, with a number of studies establishing unequivocal relationships between diet and cancer initiation and progression. Reflecting the accumulation of these data, the WHO has now stated that diet forms the secondmost preventable cause of cancer (after smoking) (3) . This impact will rise further as a result of demographic factors, and quite possibly because of changing dietary habits worldwide, which will contribute further to the projected increase in cancer incidence in developing nations. Highprofile malignancies such as breast, prostate, and colon cancer typify this scenario, in which the aetiology of the disease reflects the cumulative impact of dietary factors over an individual's lifetime (4)(5)(6) . The relationship between diet and disease is already exploited clinically, e.g. in the Selenium and Vitamin E Cancer Prevention Trial to assess the chemoprevention potential of vitamin E ...

show abstract

Section: Epigenetic Resistancesupporting

confidence: 85%

The vitamin D receptor in cancer

2008

View full text Add to dashboard Cite

show abstract

“…This butyrate-related effect of enhanced cell differentiation most likely helps maintain barrier integrity against inflammationperpetuating bacteria, and provide a possible indirect mechanism for the benefits of PF. Intriguingly, butyrate promotes cell differentiation and apoptosis in cancerous cells and cell lines while having the opposite effect in healthy colonocytes [30]. These differences may be explained by a much slower butyrate metabolism demonstrated in…”

Section: Butyratementioning

confidence: 99%

“…ALP is an enzyme thought to enact an antibacterial effect through dephosphorylation of proinflammatory lipopolysaccharide [29]. However, evidence that ALP is produced in increasing quantities as enterocytes differentiate has led to ALP secretion being used as a marker of enterocyte differentiation (that includes both transformed and primary cells) [28,30,31].…”

Section: Epithelial Barrier Functionmentioning

confidence: 99%

“…This includes monocytes, macrophages [34], enterocytes and colonocytes [35]. The vitamin D receptor (VDR) is a nuclear receptor that dimerises with the retinoid-X receptor in the presence of calcitriol, allowing it to bind to the hormone response elements that control over the expression of certain genes [30]. Accordingly, VDR mediates most of the known downstream effects of active vitamin D [33].…”

Section: Vitamin Dmentioning

confidence: 99%

“…Vitamin D up-regulates expression of several tight junction proteins, including occludin, ZO-1, ZO-2, and vinculin [37]. Vitamin D has been shown to induce the expression of intestinal alkaline phosphatase (IAP) [30] and cathelicidin [34], two anti-microbial peptides that are also markers of enterocyte differentiation [38]. There is also evidence that activation of the Vitamin D receptor can affect the Wnt signalling pathway via decreased β-catenin and increased E-cadherin activity, resulting in decreased cell division and increased differentiation in cultured cells [37].…”

Section: Vitamin Dmentioning

confidence: 99%

See 2 more Smart Citations

The effect of polymeric formula on enterocyte differentiation

et al. 2017

View full text Add to dashboard Cite

Exclusive Enteral Nutrition (EEN) is commonly used in the management of Crohn's disease (CD). Polymeric formulae (PF), comprising whole proteins along with the daily requirements of vitamins and minerals, are commonly used for EEN. The mechanism by which several weeks of PF treatment induces remission is incompletely understood and appears to be a combination of modulation of the intestinal microbiota and antiinflammatory effects on the intestinal mucosa. These include a reduction in inflammatory cytokine production and improved barrier function.The hypothesis for the current work was that PF caused an increased rate of differentiation of enterocytes at physiological concentrations. This was tested using Caco-2 cell culture and murine enteroids as in vitro models of the intestine.When Caco-2 cells were treated with PF, it caused an increase in intestinal alkaline phosphatase (IAP) expression and activity, a marker of enterocyte differentiation. This was associated with a decrease in cell proliferation and viability. Murine enteroids dissociated after several hours of exposure to PF, possibly due to interference with Wnt signalling.It was hypothesised that the observed effect of PF on Caco-2 cells might be mediated via the vitamin D receptor (VDR). However, when the activity of this receptor was reduced through use of an inhibitor, no change in PF-induced IAP activity and/or decrease in proliferation was observed. This suggests that the VDR pathway is not the primary driver of the accelerated differentiation seen in PF-treated cells.ii Acknowledgement

show abstract

The TGFβ/Smad 3‐signaling pathway is involved in butyrate‐mediated vitamin D receptor (VDR)‐expression

Daniel

Schröder

Zahn

et al. 2007

J of Cellular Biochemistry

Self Cite

View full text Add to dashboard Cite

Previously, we demonstrated the pivotal role of the vitamin D receptor (VDR) in mediating the butyrate-induced differentiation in colon cancer cells. Smad 3, a downstream component of transforming growth factor-beta (TGFbeta) signaling, has been shown to act as a coactivator of VDR and to possibly regulate the vitamin D signaling pathway. In this study, we demonstrate a distinct impact of the TGFbeta/Smad 3-signaling pathway in the butyrate-mediated VDR expression and induction of differentiation. Butyrate treatment resulted in a significant induction of the phosphorylation level of Smad 3, while the combination of butyrate and a specific TGFbeta1-antibody or a TGFbeta-receptor inhibitor considerably diminished the butyrate-induced upregulation of VDR expression. Using a specific inhibitor, we were also able to demonstrate an involvement of the p38 MAPK in the increase of Smad 3 phosphorylation following butyrate treatment, thus opening the view to further elucidate possible mechanisms mediating the upregulation of VDR expression following butyrate treatment in colon cancer cells.

show abstract

Butyrate-Induced Differentiation of Caco-2 Cells Is Mediated by Vitamin D Receptor

Cited by 48 publications

References 31 publications

The vitamin D receptor in cancer

The vitamin D receptor in cancer

The effect of polymeric formula on enterocyte differentiation

The TGFβ/Smad 3‐signaling pathway is involved in butyrate‐mediated vitamin D receptor (VDR)‐expression

Contact Info

Product

Resources

About