Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway

Ruemmele, Frank M; Schwartz, Stephen M.; Seidman, Ernest G.; Dionne, Serge; Lévy, Émile; Lentze, Michael J.

doi:10.1136/gut.52.1.94

Cited by 139 publications

(115 citation statements)

References 30 publications

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“…Different types of non-digestible carbohydrate have been shown to produce different SCFA ratios (Berggren et al 1993;Henningsson et al 2001). Several studies have shown that the acids plays a significant role in the process of inhibiting colon carcinogenesis by stimulating cell proliferation and inducing apoptosis, which in turn affects carcinogenesis (Ruemmele et al 2003;Fung et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague–Dawley rats

Pattananandecha

Sirilun

Duangjitcharoen

et al. 2016

Pharmaceutical Biology

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Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)-induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9-and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOMtreated rats fed with inulin-supplemented diet showed $1.3-and $2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as b-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary administration of inulin reduces the formation of preneoplastic lesions in the colon, possibly by altering the microecology and microbial activities on carcinogenesis.ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague–Dawley rats

Pattananandecha

Sirilun

Duangjitcharoen

et al. 2016

Pharmaceutical Biology

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“…100 Importantly, inhibitors of caspase 3 and 9, but not 8, inhibit butyrate-induced apoptosis in Caco-2 cells, 101 emphasizing the importance of the intrinsic apoptotic pathway.…”

Section: Apoptosismentioning

confidence: 99%

Section: Apoptosismentioning

confidence: 99%

“…For example, HDACi induce expression of the pro-apoptotic Bak protein, 101,102 and downregulate expression of the anti-apoptotic protein, BclX L . 101 HDACi also induce mitochondrial localization of Bax and Bak. 103 HDACi-induced apoptosis has also been shown to involve nuclear to cytoplasmic shuttling of the orphan receptor Nurr77/TR3, which in turn is linked to localization of Bax to the mitochondria and cytochrome c release.…”

Section: Apoptosismentioning

confidence: 99%

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HDACs and HDAC inhibitors in colon cancer

Mariadason¹

2008

Epigenetics

192

190

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“…Internal control experiments were performed using butyrate, a typical inducer of apoptosis in CaCo-2 cells (27). To evaluate the maximal inducible activity of caspase-3/7 in the culture system, cells were stimulated with 100 mmol/L butyrate (normoxia + butyrate, 7,911.0 ± 1,395.0, versus normoxia, 434.9 ± 81.3; P < 0.01; data not shown).…”

Section: R E S E a R C H A R T I C L E M O L M E D 1 8 : 2 9 -3 7 2mentioning

confidence: 99%

Serum from Patients Undergoing Remote Ischemic Preconditioning Protects Cultured Human Intestinal Cells from Hypoxia-Induced Damage: Involvement of Matrixmetalloproteinase-2 and -9

Zitta

Meybohm

Bein

et al. 2011

Mol Med

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Remote ischemic preconditioning (RIPC) can be induced by transient occlusion of blood flow to a limb with a blood pressure cuff and exerts multiorgan protection from ischemia/reperfusion injury. Ischemia/reperfusion injury in the intestinal tract leads to intestinal barrier dysfunction and can result in multiple organ failure. Here we used an intestinal cell line (CaCo-2) to evaluate the effects of RIPC-conditioned patient sera on hypoxia-induced cell damage in vitro and to identify serum factors that mediate RIPC effects. Patient sera (n = 10) derived before RIPC (T0), directly after RIPC (T1) and 1 h after RIPC (T2) were added to the culture medium at the onset of hypoxia until 48 h after hypoxia. Reverse transcription-polymerase chain reaction, lactate dehydrogenase (LDH) assays, caspase-3/7 assays, silver staining, gelatin zymography and Western blotting were performed. Hypoxia led to morphological signs of cell damage and increased the release of LDH in cultures containing sera T0 (P < 0.01) and T1 (P < 0.05), but not sera T2, which reduced the hypoxia-mediated LDH release compared with sera T0 (P < 0.05). Gelatin zymography revealed a significant reduction of activities of the matrixmetalloproteinase (MMP)-2 and MMP-9 in the protective sera T2 compared with the nonprotective sera T0 (MMP-2: P < 0.01; MMP-9: P < 0.05). Addition of human recombinant MMP-2 and MMP-9 to MMP-deficient culture media increased the sensitivity of CaCo-2 cells to hypoxia-induced cell damage (P < 0.05), but did not result in a reduced phosphorylation of prosurvival kinases p42/44 and protein kinase B (Akt) or increased activity of caspase-3/7. Our results suggest MMP-2 and MMP-9 as currently unknown humoral factors that may be involved in RIPC-mediated cytoprotection in the intestine.

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Butyrate induced Caco-2 cell apoptosis is mediated via the mitochondrial pathway

Cited by 139 publications

References 30 publications

Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague–Dawley rats

Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague–Dawley rats

HDACs and HDAC inhibitors in colon cancer

Serum from Patients Undergoing Remote Ischemic Preconditioning Protects Cultured Human Intestinal Cells from Hypoxia-Induced Damage: Involvement of Matrixmetalloproteinase-2 and -9

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