Butyrate impairs intestinal tumor cell induced angiogenesis by inhibiting HIF-1α nuclear translocation

Zgouras, Dimitrios; Stein, J. L.

doi:10.1016/s0016-5085(03)80666-2

Cited by 20 publications

(23 citation statements)

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“…We showed that butyrate inhibits HIF-1 activity and modulates the barrier function in the cells. Supporting our results, Zgouras et al (35) recently reported that butyrate decreases HIF-1␣ DNA-binding activity by inhibiting HIF-1␣ nuclear translocation in Caco-2 cells, which subsequently reduce VEGF secretion levels. Mariadason et al (36) reported that butyrate disrupts the intestinal barrier function under some conditions.…”

Section: Discussionsupporting

confidence: 92%

Butyrate Suppresses Hypoxia-Inducible Factor-1 Activity in Intestinal Epithelial Cells Under Hypoxic Conditions

Kushima

Unno²,

Nagata

et al. 2004

Shock

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Interaction between the products of intestinal bacteria and the intestinal epithelial cells is a key event in understanding the biological, physiological, and pathological functions of the intestinal epithelium. Here, we examined the effect of butyrate, one of the major intestinal bacterial products, on hypoxia-inducible factor-1 (HIF-1) activity under hypoxic conditions in intestinal epithelial cells. HIF-1 activity was assessed by luciferase assay using cytoplasmic extracts of intestinal epithelial cells, Caco-2, and IEC-6 cells. These cells were transiently transfected with hypoxia response element (HRE)-luciferase reporter plasmids and cultured under hypoxic conditions in the presence or absence of sodium butyrate (NaB). The effect of NaB on HRE DNA binding activity in Caco-2 cells under hypoxic conditions was assessed by electrophoretic mobility shift assay. Expression of a hypoxia-responsive gene encoding intestinal trefoil factor (ITF) in Caco-2 cells after NaB treatment was assessed using reverse-transcription PCR. The barrier function of Caco-2 cells under hypoxic conditions was also evaluated by transepithelial electrical resistance measurement. NaB suppressed up-regulation of HIF-1 transcriptional activity under hypoxic conditions in Caco-2 and IEC-6 cells. In parallel, NaB reduced HRE DNA binding activity under the same conditions. Furthermore, NaB down-regulated enhanced transcription of ITF gene. Addition of NaB under hypoxic conditions delayed recovery of transepithelial electrical resistance of the monolayers after hypoxia-reoxygenation treatment. These findings indicate that NaB suppresses HIF-1 transcriptional activity on hypoxia-responsive genes by reducing the HRE DNA binding activity under hypoxic conditions in intestinal epithelial cells.

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Section: Discussionsupporting

confidence: 92%

Butyrate Suppresses Hypoxia-Inducible Factor-1 Activity in Intestinal Epithelial Cells Under Hypoxic Conditions

Kushima

Unno²,

Nagata

et al. 2004

Shock

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“…90,91 Finally, it has also been suggested that butyrate inhibits tumourinduced angiogenesis through modulation of two angiogenesis-related proteins, vascular endothelial growth factor (VEGF) and hypoxia-inducible factor (HIF)-1a. 92 In conclusion, butyrate may have a protective role in the prevention and progression of colorectal carcinogenesis. However, the effects on apoptosis and proliferation appear to differ between normal and neoplastic tissue.…”

Section: Mechanisms Of Butyrate's Anticarcinogenic Effectmentioning

confidence: 89%

“…Furthermore, butyrate may have an inhibitory effect on tumour cell migration by inhibiting decay‐accelerating factor (DAF) expression 89 and pro‐metastatic metalloproteinase activation 90, 91 . Finally, it has also been suggested that butyrate inhibits tumour‐induced angiogenesis through modulation of two angiogenesis‐related proteins, vascular endothelial growth factor (VEGF) and hypoxia‐inducible factor (HIF)‐1α 92 …”

Section: Butyrate and Colon Carcinogenesismentioning

confidence: 99%

Review article: the role of butyrate on colonic function

Hamer¹,

Jonkers²,

Venema³

et al. 2007

Aliment Pharmacol Ther

2,217

1,612

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“…75 Butyrate modulates vascular endothelial growth factor and hypoxia-inducible factor-1a angiogenesis-related proteins, which leads to inhibition of tumor-induced angiogenesis. 76,77 It hyperinduces Wnt transcriptional activity in colorectal cancer cell lines, induces apoptosis, and may protect against colorectal cancer. 78 Butyrate reduces in vitro lymphocyte proliferation in mice and rats.…”

Section: Physiologic Significance Of Carbohydrate Fermentationmentioning

confidence: 99%

Fermentation in the Human Large Intestine

Macfarlane¹,

Macfarlane²

2011

Journal of Clinical Gastroenterology

339

117

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The human large intestine harbors a complex microbiota containing many hundreds of different bacterial species. Although structure/function relationships between different components of the microbiota are unclear, this complex multicellular entity plays an important role in maintaining homeostasis in the body. Many of the physiologic properties of the microbiota can be attributed to fermentation and the production of short-chain fatty acids (SCFAs), particularly acetate, propionate, and butyrate. In healthy people, fermentation processes are largely controlled by the amounts and different types of substrate, particularly complex carbohydrates that are accessible to bacteria in the colonic ecosystem. However, other factors impact on bacterial metabolism in the large gut, including large bowel transit time, the availability of inorganic terminal electron acceptors, such as nitrate and sulfate, and gut pH. They all affect the types and levels of SCFA that can be formed by the microbiota. This is important because to a large extent, acetate, propionate, and butyrate have varying physiologic effects in different body tissues. Prebiotics such as galactooligosaccharides together with inulins and their fructooligosaccharide derivatives have been shown to modify the species composition of the colonic microbiota, and in various degrees, to manifest several health-promoting properties related to enhanced mineral absorption, laxation, potential anticancer properties, lipid metabolism, and anti-inflammatory and other immune effects, including atopic disease. Many of these phenomena can be linked to their digestion and SCFA production by bacteria in the large gut.

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Butyrate impairs intestinal tumor cell induced angiogenesis by inhibiting HIF-1α nuclear translocation

Cited by 20 publications

References 0 publications

Butyrate Suppresses Hypoxia-Inducible Factor-1 Activity in Intestinal Epithelial Cells Under Hypoxic Conditions

Butyrate Suppresses Hypoxia-Inducible Factor-1 Activity in Intestinal Epithelial Cells Under Hypoxic Conditions

Review article: the role of butyrate on colonic function

Fermentation in the Human Large Intestine

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