Phorbol ester augments butyrate-induced apoptosis of colon cancer cells

McBain, John A.; Eastman, Alan; Simmons, David L.; Pettit, George R.; Mueller, Gerald C.

doi:10.1002/(sici)1097-0215(19960904)67:5<715::aid-ijc21>3.0.co;2-2

Cited by 22 publications

(13 citation statements)

References 24 publications

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“…A similar pattern of mechanism has been described for several cell lines including prostate cancer cell lines for the effect of phorbol ester (Blagosklonny et al, 1997). This observation possibly suggests that a combination of phorbol ester and butyrates may have an additive effect on tumour cells (McBain et al, 1996;Rahmani et al, 2002).…”

Section: Discussionsupporting

confidence: 76%

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

et al. 2004

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Histone deacetylase inhibitors (HDACs) are known to exhibit antiproliferative effects on various carcinoma cells. In this study, the in vivo efficiency of two HDACs, sodium butyrate and tributyrin, on prostate cancer growth inhibition were investigated. To gain an insight into the possible underlying pathways, cell culture experiments were performed focusing on the expression of p21, Rb and cmyc. For in vivo testing, prostate cancer cell lines (PC3 and TSU-Pr1) were seeded on the chorioallantois membrane (CAM) and implanted in a xenograft model using nude mice. Standard Western blot analysis was performed for protein expression of p21, Rb and c-myc in HDAC-treated vs untreated prostate cancer cells. Both sodium butyrate and tributyrin had a considerable treatment effect on microtumours on the chicken egg at already very low concentrations of 0.1 mM. Tributyrin-treated tumours showed the strongest effect with 38% apoptotic nuclei in the prostate cancer cell line PC3. In the mouse model, there was almost no difference between sodium butyrate and tributyrin. In untreated animals the tumours were almost double the size 4 weeks after implantation. Tumours of the treatment groups had a significantly lower percentage of Ki-67-positive-stained nuclei. As demonstrated by Western blot analysis, these effects seem to be independent of p53 status and a pathway via p21 -Rb -c-myc is possibly involved. In this study we have demonstrated a substantial in vivo treatment effect, which can be induced by the application of sodium butyrate or the orally applicable tributyrin in human prostate cancer. The given results may provide the rationale to apply these drugs in well-controlled clinical trials in patients being at high risk of recurrence after specific therapy or in patients with locally or distant advanced prostate cancer.

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Section: Discussionsupporting

confidence: 76%

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

et al. 2004

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“…The differences in butyrate modulation of Wnt signaling between these cell lines may at least partially explain the differences between them in physiologic responsiveness to butyrate, 35,39 -41,44 possibly including the relative resistance of HCT-116 cells to butyrate-induced cell death. 35,42 This possibility is supported by a recent report that has demonstrated a link between Wnt signaling and apoptosis; activation of the Wnt signaling pathway was shown to block drug-induced apoptosis in a manner dependent on BCT-dependent transcriptional activity. 66 The SW620 and HCT-116 cell lines may represent subtypes of colonic tumors that differ in their levels of Wnt signaling and responsiveness of Wnt signaling to chemopreventive and therapeutic reagents, as well as in their Wnt signaling-dependent phenotype.…”

Section: Discussionmentioning

confidence: 80%

“…11,17 In contrast to the SW620 line, HCT-116 cells are characterized as having a high level of resistance to butyrate, 35 as treatment with 5 mM butyrate induces reversible growth arrest without significant cell death. 35,42 To determine whether the downregulation of Tcf-TK in butyrate-treated SW620 cells is a general phenomenon, we repeated the transfection in HCT-116 cells. Unlike SW620 cells, butyrate treatment of HCT-116 cells resulted in a marked enhancement of BCT activity from Tcf-TK.…”

Section: Butyrate Modulation Of Wnt Signaling Is Promoter-and Cell-tymentioning

confidence: 99%

“…28 -36 Butyrate has been shown to stimulate these processes in a number of cell lines, including colonic carcinoma cells. [37][38][39][40][41][42][43] In a previous report, we have demonstrated that, in SW620 colon carcinoma cells, sodium butyrate upregulates expression from a Tcf-fos reporter in an APC-independent manner. 44 Therefore, some effects of butyrate on growth arrest, differentiation and/or apoptosis may be due to its ability to modulate the Wnt signaling pathway.…”

mentioning

confidence: 99%

“…17 The second line employed was APC-wild type HCT-116; these cells have been reported to undergo reversible growth arrest, but no significant cell death, after treatment with 5 mM butyrate. 35,42 The HCT-116 line contains mutant ␤-catenin, 12 low levels of BCT complexes and high levels of free Tcf. 11,17 One class of BCT-dependent promoters that we have used was represented by the minimal fos or minimal TK promoters, linked to Tcf binding sites (Tcf-fos and Tcf-TK, respectively), which are dependent on the transactivation function of ␤-catenin for high levels of expression.…”

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confidence: 99%

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Cell type‐ and promoter‐dependent modulation of the Wnt signaling pathway by sodium butyrate

Bordonaro

Lazarova

Augenlicht

et al. 2001

Intl Journal of Cancer

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The Wnt signaling pathway modulates the transcription of genes linked to proliferation, differentiation and tumor progression. ␤-Catenin-Tcf (BCT)-dependent Wnt signaling is influenced by the short-chain fatty acid sodium butyrate, which induces growth arrest and/or maturation of colonic carcinoma cells. We have compared the effects of sodium butyrate on BCT-dependent signaling in 2 colon carcinoma cell lines that differ in their physiologic response to butyrate, with SW620 cells responding to butyrate by undergoing terminal differentiation and apoptosis, and HCT-116 cells undergoing reversible growth arrest, but no significant apoptotic cell death. Furthermore, these colon carcinoma cell lines differ in their mechanism of Wnt pathway activation, with adenomatous polyposis coli (APC) mutant SW620 cells having high levels of BCT complexes and APC wild-type HCT-116 cells having mutant ␤-catenin, low levels of BCT complexes and correspondingly higher levels of free Tcf. We have demonstrated that in SW620 cells, butyrate downregulates BCT-dependent expression of the Tcf-TK, matrilysin and cyclin D1 promoters, whereas in HCT-116 cells, butyrate upregulates expression of these promoters. Cotransfection with expression vectors that interfere with the Wnt pathway suggests that butyrate enhances BCT complex-DNA binding. Butyrate reduces the expression of Tcf4 in HCT-116 cells, consistent with the induction by butyrate of Tcf-repressible promoters in these cells. These findings indicate that sodium butyrate modulates the Wnt pathway in SW620 and HCT-116 cells in a different manner and that these differences have consequences for promoter activity that may influence the physiologic response to butyrate.

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Short-chain fatty acids reduce expression of specific protein kinase C isoforms in human colonic epithelial cells

et al. 2000

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LIM1215 colon cancer cells were used as a model of human colonic epithelium to examine the effects of butyrate on protein kinase C (PKC) activity and isoform expression. On Western blot analysis, LIM1215 cells express the PKC isoforms alpha, beta, epsilon, zeta, and lambda, but not gamma, straight theta, or micro. Treatment with 2 mM butyrate for 48 h reduced cellular PKC activity up to 50% and specifically reduced the expression of PKC alpha and PKC epsilon. Similar results were obtained using Caco-2 colon cancer cells. These effects were neither a consequence of the induction of differentiation itself nor the result of direct or indirect activation of PKC. Although dependent on gene transcription and protein synthesis, the effect was not due to a reduction in the synthesis of PKC protein. Butyrate's effect was independent of its beta-oxidation but was mimicked, at least in part, by trichostatin A, an inhibitor of histone deacetylase.

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Phorbol ester augments butyrate-induced apoptosis of colon cancer cells

Cited by 22 publications

References 24 publications

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

Sodium butyrate and tributyrin induce in vivo growth inhibition and apoptosis in human prostate cancer

Cell type‐ and promoter‐dependent modulation of the Wnt signaling pathway by sodium butyrate

Short-chain fatty acids reduce expression of specific protein kinase C isoforms in human colonic epithelial cells

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