Bile acid-induced proliferation of a human colon cancer cell line is mediated by transactivation of epidermal growth factor receptors

Cheng, Kunrong; Raufman, Jean‐Pierre

doi:10.1016/j.bcp.2005.07.023

Cited by 131 publications

(162 citation statements)

References 61 publications

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“…Colonic epithelial cells are physiologically exposed to activators of cholinergic receptors and protein kinase C, such as secondary bile acids, reported to activate muscarinic receptors and transactivate epidermal growth factor signaling (33,34). We first described muscarinic M 3 receptors on HT-29 human colon carcinoma cells coupled to phosphoinositide breakdown and second messenger signaling, and others have shown the role of M 3 receptors mediating proliferative responses induced by bile acids (35,36).…”

Section: Discussionmentioning

confidence: 99%

Butyrate-induced alterations of phosphoinositide metabolism, protein kinase C activity and reduced CD44 variant expression in HT-29 colon cancer cells

Kopp¹,

Fichter²,

Assert³

et al. 2009

Int J Mol Med

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Abstract. Initiation of cell growth and neoplastic transformation frequently involves activation of growth factor receptor-coupled tyrosine kinases and stimulation of the phosphoinositide second messenger system. Altered expression of CD44 variants was reported in several malignant tumor types with possible implications for tumor progression and prognosis. CD44 variant expression was reported to be associated with second messenger activation and differentiation. We therefore investigated the effects of butyrateinduced short-term differentiation on phosphoinositide signaling, phospholipase C and protein kinase C activity and alteration of CD44 variant expression in human HT-29 colon carcinoma cells. HT-29 cells were cultured with sodium butyrate for 6 days. Phosphoinositide turnover was measured by [32 P]orthophosphate incorporation and phospholipase C activity by determination of the release of [ 3 H]inositolphosphates from [ 3 H]myoinositol prelabeled cells. Protein kinase C activity was determined by histone III-S phosphorylation, PKC subtype expression by RNase protection analysis, and CD44 variant expression was determined by RT-PCR using variant-specific primers. Treatment of HT-29 human colon carcinoma cells with sodium butyrate caused a dose-dependent inhibition of cell proliferation (IC 50 , 2.5 mM) with morphologic signs of an enterocytic differentiation following 6 days of treatment. The phosphoinositide turnover as determined by 32 P-incorporation under non-equilibrium conditions showed a 30-40% inhibition of labeled phosphoinositides and phosphatidic acid and a dose-dependent inhibition of cholinergically stimulated phospholipase C activity as a secondary event following butyrate-induced enterocytic differentiation. However, long-term incubation of HT-29 cells with phorbol ester or an inhibitor of classical and novel PKC subtypes did not affect cell proliferation. In butyrate-treated HT-29 cells activation of calcium-dependent protein kinase C by cholinergic stimulation or phorbolester treatment induced an increase in membrane-bound cPKC activity, while expression of distinct high-molecular CD44 variant transcripts v3 (670 bp), v5 (940 bp) and v8 (535 bp) were drastically reduced after butyrate pretreatment. Enterocytic differentiation of HT-29 colon carcinoma cells seems to be associated with alterations in phosphoinositide resynthesis, phospholipase C activity and ligand/receptorinduced PKC translocation. The observed reduction of distinct high-molecular CD44v3, v5 and v8 variants following butyrate-induced differentiation indicates an association of specific CD44 variant expression with the malignant phenotype of HT-29 colon cancer cells, thus being possible targets for new diagnostic and therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Butyrate-induced alterations of phosphoinositide metabolism, protein kinase C activity and reduced CD44 variant expression in HT-29 colon cancer cells

Kopp¹,

Fichter²,

Assert³

et al. 2009

Int J Mol Med

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“…The detergent properties of DCA (but not CA) cause membrane perturbations leading to the release of arachidonic acid, which is converted by the enzymes cyclooxygenase 2 (COX-2) and lipooxygenase, to proinflammatory and pro-angiogenic prostaglandins, and reactive oxygen species which damage DNA and inhibit DNA repair enzymes. 87,88 DCA also induces COX-2 expression through transactivation of the epidermal growth factor receptor, 87,89 and activates the b-catenin cell-signaling pathway resulting in colon cancer cell proliferation and invasiveness. 90 Notably, a large body of published work demonstrates the effectiveness of non-steroidal anti-inflammatory drugs in significantly reducing polyp formation and reducing CRC risk by inhibiting the activity of COX-2.…”

Section: Deoxycholic Acid and Colon Cancermentioning

confidence: 99%

Taurocholic acid metabolism by gut microbes and colon cancer

Ridlon¹,

Wolf²,

Gaskins³

2016

Gut Microbes

264

229

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Colorectal cancer (CRC) is one of the most frequent causes of cancer death worldwide and is associated with adoption of a diet high in animal protein and saturated fat. Saturated fat induces increased bile secretion into the intestine. Increased bile secretion selects for populations of gut microbes capable of altering the bile acid pool, generating tumor-promoting secondary bile acids such as deoxycholic acid and lithocholic acid. Epidemiological evidence suggests CRC is associated with increased levels of DCA in serum, bile, and stool. Mechanisms by which secondary bile acids promote CRC are explored. Furthermore, in humans bile acid conjugation can vary by diet. Vegetarian diets favor glycine conjugation while diets high in animal protein favor taurine conjugation. Metabolism of taurine conjugated bile acids by gut microbes generates hydrogen sulfide, a genotoxic compound. Thus, taurocholic acid has the potential to stimulate intestinal bacteria capable of converting taurine and cholic acid to hydrogen sulfide and deoxycholic acid, a genotoxin and tumor-promoter, respectively.

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“…Moreover, inhibition of BRCA-1 by relatively high DCA concentrations contributes to defective DNA repair [76] . Recently DCA and LCA (in conjugated form) were shown to elicit transactivation of the epidermal growth factor receptor via interaction with muscarinic receptors and phosphorylation of ERK [77] . Another gene target of DCA via ERK is the tumor marker EphA2 receptor protein tyrosine kinase [78] .…”

Section: Ba and Colorectal Cancermentioning

confidence: 99%

Intestinal bile acid physiology and pathophysiology

Martínez‐Augustin¹,

Medina²

2008

WJG

138

114

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Bile acids (BAs) have a long established role in fat digestion in the intestine by acting as tensioactives, due to their amphipathic characteristics. BAs are reabsorbed very efficiently by the intestinal epithelium and recycled back to the liver via transport mechanisms that have been largely elucidated. The transport and synthesis of BAs are tightly regulated in part by specific plasma membrane receptors and nuclear receptors. In addition to their primary effect, BAs have been claimed to play a role in gastrointestinal cancer, intestinal inflammation and intestinal ionic transport. BAs are not equivalent in any of these biological activities, and structural requirements have been generally identified. In particular, some BAs may be useful for cancer chemoprevention and perhaps in inflammatory bowel disease, although further research is necessary in this field. This review covers the most recent developments in these aspects of BA intestinal biology.

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Bile acid-induced proliferation of a human colon cancer cell line is mediated by transactivation of epidermal growth factor receptors

Cited by 131 publications

References 61 publications

Butyrate-induced alterations of phosphoinositide metabolism, protein kinase C activity and reduced CD44 variant expression in HT-29 colon cancer cells

Butyrate-induced alterations of phosphoinositide metabolism, protein kinase C activity and reduced CD44 variant expression in HT-29 colon cancer cells

Taurocholic acid metabolism by gut microbes and colon cancer

Intestinal bile acid physiology and pathophysiology

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