Butyrate- but not TGFβ1-induced apoptosis of colorectal adenoma cells is associated with increased expression of the differentiation markers E-cadherin and alkaline phosphatase

Butt, Alison J.; Hague, Angela; Paraskeva, Christos

doi:10.1038/sj.cdd.4400293

Cited by 23 publications

(16 citation statements)

References 45 publications

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“…On treatment with NaBt, an analogous level of induction of both differentiation markers (ALP and E-cadherin) was detected in both adenoma-and carcinomaderived cell lines, indicating that an increase in differentiation was detectable in all cell lines (the tumorigenic cell lines PC/AA/C1/SB10 and PC/JW2 as well as the non-tumorigenic PC/AA/C1, S/RG/C2 cells) (Butt et al, 1997). Additionally it has been established using FACs analysis that the G 1 /S ratio increases in a dose-dependent manner in the colorectal cell lines used in our study after 48 hours of NaBt treatment (approximately 1.5-3.2 fold, depending on cell line; Butt, 1996). Therefore the PC/AA/C1 adenoma cells and their tumorigenic derivative PC/AA/C1/SB10 cells were treated with doses of sodium butyrate (0-3 mM for 48 hours) which had previously been shown to induce differentiation, and the Rb protein expression determined by Western analysis.…”

Section: Treatment With the Differentiation Agent Sodium Butyrate Resmentioning

confidence: 84%

“…The short-chain fatty acid sodium butyrate (NaBt), a natural fermentation product of dietary fibre (Cummings, 1981) has been found to induce differentiation in a number of different cell types including colonic cells (Leder and Leder, 1975;Prasad and Sinha, 1976). Furthermore, it has previously been established that NaBt can induce differentiation in colorectal cell lines, and this induction of differentiation is evidenced by increased expression of the differentiation markers alkaline phosphatase (ALP) and E-cadherin (Butt et al, 1997). On treatment with NaBt, an analogous level of induction of both differentiation markers (ALP and E-cadherin) was detected in both adenoma-and carcinomaderived cell lines, indicating that an increase in differentiation was detectable in all cell lines (the tumorigenic cell lines PC/AA/C1/SB10 and PC/JW2 as well as the non-tumorigenic PC/AA/C1, S/RG/C2 cells) (Butt et al, 1997).…”

Section: Treatment With the Differentiation Agent Sodium Butyrate Resmentioning

confidence: 99%

“…Furthermore, it has previously been established that NaBt can induce differentiation in colorectal cell lines, and this induction of differentiation is evidenced by increased expression of the differentiation markers alkaline phosphatase (ALP) and E-cadherin (Butt et al, 1997). On treatment with NaBt, an analogous level of induction of both differentiation markers (ALP and E-cadherin) was detected in both adenoma-and carcinomaderived cell lines, indicating that an increase in differentiation was detectable in all cell lines (the tumorigenic cell lines PC/AA/C1/SB10 and PC/JW2 as well as the non-tumorigenic PC/AA/C1, S/RG/C2 cells) (Butt et al, 1997). Additionally it has been established using FACs analysis that the G 1 /S ratio increases in a dose-dependent manner in the colorectal cell lines used in our study after 48 hours of NaBt treatment (approximately 1.5-3.2 fold, depending on cell line; Butt, 1996).…”

Section: Treatment With the Differentiation Agent Sodium Butyrate Resmentioning

confidence: 99%

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Transcriptional down-regulation of the retinoblastoma protein is associated with differentiation and apoptosis in human colorectal epithelial cells

et al. 2001

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SummaryThe aim of this study was to investigate the regulation of Rb protein expression in relation to increased differentiation and induction of apoptosis in colonic epithelial cells. In vivo, Rb protein expression was found to be down-regulated towards the top of the normal colonic crypt, coincident with the region of differentiation and apoptosis, but highly expressed in colonic carcinoma tissue. Using in vitro models to study the regulation of Rb expression in pre-malignant colonic epithelial cells, we have been able to show for the first time that Rb protein expression is transcriptionally down-regulated in differentiated pre-malignant cells (in post-confluent cultures) but not in malignant colorectal epithelial cells. Furthermore, suppression of rb protein function by the HPV-E7 viral oncoprotein increased both spontaneous and DNA damage-induced apoptosis. These results suggest that Rb is able to act as a survival factor in colonic epithelial cells by suppressing apoptosis, and that over-expression of pRb in colorectal tumour cells can cause a loss of sensitivity to apoptotic signalling, resulting in aberrant cell survival and resistance to therapy. targeted inactivation of the RB-1 gene in mouse embryonic fibroblasts induces apoptosis. Therefore, pRb appears to suppress apoptosis in some cell systems, perhaps through the sequestration of the E2F-1 protein, which can induce apoptosis if over-expressed (Qin et al, 1994;Field et al, 1996). In this case, pRb needs to be removed or inactivated before apoptosis can occur. To support this, a 30 kD protein has been detected in apoptotic cells harvested from colon tumour cell lines, CMSV40 fibroblasts and BJA-B lymphocyte cells, suggesting that the Rb protein is cleaved during the apoptotic process (Browne et al, 1994;An and Dou, 1996). Furthermore, cleavage at the C-terminus of pRb results in a p100 and ~5 kDa polypeptide (Chen et al, 1997). The p100 Rb protein can still bind to E2F-1 and inhibit E2F-mediated transcriptional activity, but its anti-apoptotic function is reduced, perhaps through its inability to bind to the oncogene MDM2. Thus the growthsuppressive and anti-apoptotic functions of pRb appear to be distinct from one another. The notion that pRb functions can be separated from one another has been explored previously, and experimental evidence indicates that the multiple functions of pRb can be genetically uncoupled, providing distinct functions in cellcycle control or in tissue-specific gene expression during differentiation (reviewed in Yee et al, 1998). Mice with mutations of the N-terminal region of Rb protein exhibit defects in muscle differentiation, whilst retaining the ability to bind to E2F (Riley et al, 1997). Conversely, cells with pRb mutations in the pocket domain are able to differentiate normally even when E2F binding is abrogated (Sellers et al, 1998).The functional loss of the Rb protein, by deletion or mutation, has been implicated not only in retinoblastoma, but in many types of tumour, including bladder, breast, lung and ovarian ca...

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Section: Treatment With the Differentiation Agent Sodium Butyrate Resmentioning

confidence: 84%

Section: Treatment With the Differentiation Agent Sodium Butyrate Resmentioning

confidence: 99%

Section: Treatment With the Differentiation Agent Sodium Butyrate Resmentioning

confidence: 99%

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Transcriptional down-regulation of the retinoblastoma protein is associated with differentiation and apoptosis in human colorectal epithelial cells

et al. 2001

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“…The b-catenin/Tcf-4 pathway is considered to be the most important one controlling the switch between cellular differentiation and proliferation in intestinal epithelial cells. Induction of differentiation in HT29 cells by butyrate was observed to be accompanied by the upregulation of p21 and p53 [19]. In another study, the relationship between butyrate-mediated growth inhibition and induction of a more differentiated phenotype was investigated in a set of adenoma-derived cell lines.…”

Section: Discussionmentioning

confidence: 96%

Butyrate-Induced Cell Death and Differentiation Are Associated with Distinct Patterns of ROS in HT29-Derived Human Colon Cancer Cells

et al. 2009

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To investigate the role of reactive oxygen species (ROS) induced by butyrate in tumor cells, we compared HT29R, an HT29-derived human colon cancer cell line refractory to butyrate-induced cell differentiation but highly sensitive to cell death, with the differentiation-positive HT29-12 and HT29-21 cell lines (exhibiting low sensitivity to butyrate-induced cell death), with respect to levels of butyrate-induced free radicals (FRs), ROS, and H(2)O(2). Dose-dependent increase of FRs (as determined by electron spin resonance spectroscopy) and ROS (dichlorofluorescein assay) was induced in HT29R, but not in HT29-12 and HT29-21 cells, where, in contrast to HT29R, a dose-dependent increase of H(2)O(2) release (phenol red assay) was induced by butyrate. The mode of butyrate-induced cell death in HT29R cells was of a mixed type with necrosis predominating, which, however, switched to apoptosis as the major type of cell death in the presence of the drugs 1,5-dihydroxyisoquinoline, resveratrol, or cyclosporine A. The results suggest that FRs and ROS induced by butyrate in HT29R cells are products of cell death, while H(2)O(2) induced in HT29-12 and HT29-21 cells is functionally related to cell differentiation.

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“…We found that RNA interference-mediated inhibition of vimentin expression resulted in reemergence of keratin gene expression in cell culture and the production of smaller, more differentiated tumors in athymic mice, suggesting potential for development as a treatment modality. Pharmacology-based differentiation therapies have been developed by others, including the use of retinoids (46 -48) and butyrates (49). Combination therapy of retinoid acid receptor and retinoid X receptor agonists with chemotherapeutic drugs has shown some promise clinically in the treatment of lung cancer (50).…”

Section: Discussionmentioning

confidence: 99%

Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility

Paccione

Miyazaki

Patel

et al. 2008

Molecular Cancer Therapeutics

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At later stages of tumor progression, epithelial carcinogenesis is associated with transition to a mesenchymal phenotype, which may contribute to the more aggressive properties of cancer cells and may be stimulated by growth factors such as epidermal growth factor and transforming growth factor-B. Previously, we found that cells derived from a nodal metastatic squamous cell carcinoma are highly proliferative and motile in vitro and tumorigenic in vivo. In the current study, we have investigated the role of vimentin in proliferation and motility. Cells derived from nodal metastasis express high levels of vimentin, which is undetectable in tumor cells derived from a synchronous primary lesion of tongue. Vimentin expression was enhanced by epidermal growth factor and transforming growth factor-B both independently and in combination. Use of RNA interference resulted in the generation of stable cell lines that express constitutively low levels of vimentin. RNA interference-mediated vimentin knockdown reduced cellular proliferation, migration, and invasion through a basement membrane substitute by 3-fold compared with nontargeting controls. In addition, cells with reduced vimentin reexpressed differentiation-specific keratins K13, K14, and K15 as a result of increased gene transcription as judged by quantitative PCR and promoterreporter assays. Furthermore, cells in which vimentin expression was reduced showed a greatly decreased tumorigenic potential, as tumors developing from these cells were 70% smaller than those from control cells. The data suggest that reversal of the mesenchymal phenotype by inhibiting vimentin expression results in reexpression of epithelial characteristics and reduced tumor aggressiveness. [Mol Cancer Ther 2008;7(9):2894 -903]

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Butyrate- but not TGFβ1-induced apoptosis of colorectal adenoma cells is associated with increased expression of the differentiation markers E-cadherin and alkaline phosphatase

Cited by 23 publications

References 45 publications

Transcriptional down-regulation of the retinoblastoma protein is associated with differentiation and apoptosis in human colorectal epithelial cells

Transcriptional down-regulation of the retinoblastoma protein is associated with differentiation and apoptosis in human colorectal epithelial cells

Butyrate-Induced Cell Death and Differentiation Are Associated with Distinct Patterns of ROS in HT29-Derived Human Colon Cancer Cells

Keratin down-regulation in vimentin-positive cancer cells is reversible by vimentin RNA interference, which inhibits growth and motility

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