Bile Acids Reduce the Apoptosis-Inducing Effects of Sodium Butyrate on Human Colon Adenoma (AA/C1) Cells: Implications for Colon Carcinogenesis

McMILLAN, Lorna; Butcher, Stephen K.; Wallis, Yvonne; Neoptolemos, John P.; Lord, Janet M.

doi:10.1006/bbrc.2000.2899

Cited by 40 publications

(30 citation statements)

References 22 publications

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“…As shown previously (Hague et al, 1993;McMillan et al, 2000), sodium butyrate (6 mM) induced a significant increase in apoptosis in AA/C1 adenoma cells (Po0.005; Figure 1). In contrast, 10 mM UDCA had no effect on spontaneous apoptosis of AA/C1, but did inhibit butyrate-induced apoptosis (Figure 1).…”

Section: Resultssupporting

confidence: 86%

“…We confirm here that the secondary bile acid UDCA was able to activate PKC in whole cells (Huang et al, 1992) and show that this action was restricted to the classical PKC isoenzyme PKC-a. Although UDCA was the focus of this study, we have also shown that other bile acids can inhibit butyrate-induced apoptosis, including CDCA (McMillan et al, 2000), and this bile acid also activates PKC-a (data not shown). Interestingly, the literature suggests that PKC-a has a predominantly antiapoptotic role (Deacon et al, 1997).…”

Section: Discussionmentioning

confidence: 83%

“…For example, PKC-a is inhibited during ceramide-induced apoptosis (Lee et al, 1996) and expression of a dominant-negative PKC-a induced apoptosis in CHO cells (Whelan and Parker, 1998). Thus, those bile acids known to promote cell proliferation and inhibit butyrate-induced apoptosis, that is, UDCA, CDCA and DCA (Mahmoud et al, 1999;McMillan et al, 2000), are likely to be mediated by the activation of PKC-a. This proposal is supported by the ability of the PKC inhibitor Gö6976 to block the proliferative effects of UDCA on AA/ C1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…We have shown previously that human adenoma cells, AA/C1, treated with physiological levels of bile acids showed increased proliferation (McMillan et al, 2000). Butyrate induced apoptosis in AA/C1 cells (Hague et al, 1993;McMillan et al, 2000) and addition of bile acids to these cells reduced the level of apoptosis, although this effect could be overcome by increasing the level of butyrate (McMillan et al, 2000). Therefore, these two dietary factors interact at the cellular level and the protective effect of butyrate may relate both to its apoptosis-inducing effect per se and its ability to modify the antiapoptotic, proliferative effects of secondary bile acids.…”

mentioning

confidence: 90%

“…For example, butyrate is known to modify colonic pH and inhibit the colonic bacteria responsible for the production of bile acids (MacDonald et al, 1978). We have shown previously that human adenoma cells, AA/C1, treated with physiological levels of bile acids showed increased proliferation (McMillan et al, 2000). Butyrate induced apoptosis in AA/C1 cells (Hague et al, 1993;McMillan et al, 2000) and addition of bile acids to these cells reduced the level of apoptosis, although this effect could be overcome by increasing the level of butyrate (McMillan et al, 2000).…”

mentioning

confidence: 99%

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Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

et al. 2003

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Butyrate, produced in the colon by fermentation of dietary fibre, induces apoptosis in colon adenoma and cancer cell lines, which may contribute to protection against colorectal cancer. However, butyrate is present in the colon along with other dietary factors, including unconjugated bile acids, which are tumour promoters. We have shown previously that the proapoptotic effects of butyrate on AA/C1 human adenoma cells were reduced in the presence of bile acids. To determine the cellular basis of this interaction, we examined the effects of butyrate and the secondary bile acid ursodeoxycholic acid (UDCA) on signalling pathways known to regulate apoptosis using AA/C1 cells. Butyrate activated PKC-d and p38 MAP (mitogen-activated protein) kinase, whereas UDCA activated PKC-a and p42/44 MAP kinase. Butyrate treatment also resulted in the caspase-3-mediated proteolysis of PKC-d. Butyrate-induced apoptosis was reduced by inhibitors of PKC-d (Rottlerin), p38 MAP kinase (SB202190) and caspase 3 (DEVD-fmk), whereas the proliferative/survival effects of UDCA were blocked by inhibitors of PKC-a (Gö 6976) and MEK 1 (PD98059). The effects of butyrate and bile acids are therefore mediated by the differential activation of signalling pathways that are known to regulate apoptosis.

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Section: Resultssupporting

confidence: 86%

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 90%

mentioning

confidence: 99%

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Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

et al. 2003

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Deoxycholic acid promotes the growth of colonic aberrant crypt foci

Flynn

Montrose

Swank

et al. 2006

Molecular Carcinogenesis

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AKR/J mice are resistant to the tumorigenic properties of the colon carcinogen, azoxymethane (AOM). Following AOM exposure, limited numbers of preneoplastic lesions, referred to as aberrant crypt foci (ACF), are formed in the colon, and their progression to tumors rarely occurs. To determine whether genetic resistance can be overcome by exposure to a dietary tumor promoter, AOM-exposed AKR/J mice were fed a diet containing 0.25% deoxycholic acid (DCA). DCA exposure was begun 1 wk prior to or 1 wk after tumor initiation with AOM. Mice placed on the DCA diet prior to AOM treatment developed a significantly higher multiplicity of ACF compared to AOM-exposed mice fed a control diet (15.50 +/- 0.96 vs. 6.17 +/- 0.48, respectively; P < 0.05). When DCA exposure was begun after AOM treatment (post-initiation), ACF formation was further enhanced (34.00 +/- 1.22). Interestingly, increased numbers of ACF were associated with the presence of nuclear beta-catenin, assessed by immunohistochemistry. While approximately 33% of ACF from mice exposed to DCA prior to AOM treatment contained positive nuclear beta-catenin staining, approximately 77% of ACF from mice fed DCA after AOM were positive. Accumulation of nuclear beta-catenin was not associated with a loss of E-cadherin from the plasma membrane, although loss of APC staining was a consistent feature of most AOM-induced ACF, regardless of DCA exposure. These results demonstrate that exposure to DCA, an important digestive component, is sufficient to sensitize the resistant AKR/J colon to formation of high-grade dysplasia, and that nuclear translocation of beta-catenin may play an important role in this process.

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Bile Acids and Cholestatic Liver Disease 2: Primary Sclerosing Cholangitis

Nakazawa

2017

Bile Acids in Gastroenterology

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Bile Acids Reduce the Apoptosis-Inducing Effects of Sodium Butyrate on Human Colon Adenoma (AA/C1) Cells: Implications for Colon Carcinogenesis

Cited by 40 publications

References 22 publications

Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

Opposing effects of butyrate and bile acids on apoptosis of human colon adenoma cells: differential activation of PKC and MAP kinases

Deoxycholic acid promotes the growth of colonic aberrant crypt foci

Bile Acids and Cholestatic Liver Disease 2: Primary Sclerosing Cholangitis

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