Altered gene expression and miRNA expression associated with cancerous IEC-6 cell transformed by MNNG

Zhang, Bo; Wang, Xukai; Wang, Yan

doi:10.1186/1756-9966-28-56

Cited by 12 publications

(5 citation statements)

References 37 publications

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“…It is known that cells mutated under MNNG exposure can acquire increased cellular proliferation capacity through changes in oncogene and miRNA expressions [34]. On the other hand, a delay in the G 2 /M phase of the cell-cycle was reported in colon cancer cells exposed to MNNG [35].…”

Section: Discussionmentioning

confidence: 99%

Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model

et al. 2012

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The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N’-nitro-N-nitrosoguanidine (MNNG) as models. Fluoxetine increased the percentage of HT29 cells in the G0/G1 phase of cell-cycle, and the expression of p27 protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and stromal areas. It was accompanied by a reduction of VEGF expression and of the number of cells with angiogenic potential, such as CD133, CD34, and CD31-positive cell clusters. Taken together, our findings suggest that fluoxetine treatment targets steps of early colon carcinogenesis. This confirms its protective potential, explaining at least partially the lower colon cancer risk under antidepressant therapy.

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Section: Discussionmentioning

confidence: 99%

Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model

et al. 2012

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“…Total protein was used to assess HDAC1, DNMT1, DNMT3A and DNMT3B, survivin, anti-acetylated H3 and γ-H2AX. Total protein analysis instead of acid extraction was performed to determine anti-acetylated H3 and γ-H2AX levels as they have been determined in the similar manner as has been previously reported [21, 22]. Antibodies against p21 and anti-acetylated H3 (Millipore, CA, USA), HDAC1, DNMT1, NF-κB-p65 (Abcam), p53, survivin, DNMT3A, DNMT3B (Santacruz Biotechnology) and γ-H2AX (Cell Signaling) were used to probe the corresponding proteins.…”

Section: Methodsmentioning

confidence: 99%

Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

Saldanha

Kala

Tollefsbol

2014

Experimental Cell Research

112

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Bioactive compounds are considered safe and have been shown to alter genetic and epigenetic profiles of tumor cells. However, many of these changes have been reported at molecular concentrations higher than physiologically achievable levels. We investigated the role of the combinatorial effects of epigallocatechin gallate (EGCG), a predominant polyphenol in green tea, and sodium butyrate (NaB), a dietary microbial fermentation product of fiber, in the regulation of survivin, which is an overexpressed anti-apoptotic protein in colon cancer cells. For the first time, our study showed that the combination treatment induced apoptosis and cell cycle arrest in RKO, HCT-116 and HT-29 colorectal cancer cells. This was found to be regulated by the decrease in HDAC1, DNMT1, survivin and HDAC activity in all three cell lines. A G2/M arrest was observed for RKO and HCT-116 cells, and G1 arrest for HT-29 colorectal cancer cells for combinatorial treatment. Further experimentation of the molecular mechanisms in RKO colorectal cancer cells revealed a p53-dependent induction of p21 and an increase in nuclear factor kappa B (NF-κB)-p65. An increase in double strand breaks as determined by gamma-H2A histone family member X (γ-H2AX) protein levels and induction of histone H3 hyperacetylation was also observed with combination treatment. Further, we observed a decrease in global CpG methylation. Taken together, these findings suggest that at low and physiologically achievable concentrations, combinatorial EGCG and NaB are effective in promoting apoptosis, inducing cell cycle arrest and DNA-damage in colorectal cancer cells.

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“…Looking at our in vitro results and the chemopreventive activity of FLX against MNNG-induced dysplasia through reduced epithelial proliferation, it seems possible that FLX promotes these effects by controlling cell-cycle progression in vivo. It is known that cells mutated under MNNG exposure can acquire increased cellular proliferation capacity through changes in oncogene and miRNA expressions [34]. On the other hand, a delay in the G 2 /M phase of the cell-cycle was reported in colon cancer cells exposed to MNNG [35].…”

Section: Discussionmentioning

confidence: 99%

Correction: Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model

Kannen¹,

Hintzsche²,

Zanette³

et al. 2013

PLoS ONE

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The antidepressant fluoxetine has been under discussion because of its potential influence on cancer risk. It was found to inhibit the development of carcinogen-induced preneoplastic lesions in colon tissue, but the mechanisms of action are not well understood. Therefore, we investigated anti-proliferative effects, and used HT29 colon tumor cells in vitro, as well as C57BL/6 mice exposed to intra-rectal treatment with the carcinogen N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) as models. Fluoxetine increased the percentage of HT29 cells in the G 0 /G 1 phase of cell-cycle, and the expression of p27 protein. This was not related to an induction of apoptosis, reactive oxygen species or DNA damage. In vivo, fluoxetine reduced the development of MNNG-induced dysplasia and vascularization-related dysplasia in colon tissue, which was analyzed by histopathological techniques. An anti-proliferative potential of fluoxetine was observed in epithelial and stromal areas. It was accompanied by a reduction of VEGF expression and of the number of cells with angiogenic potential, such as CD133, CD34, and CD31-positive cell clusters. Taken together, our findings suggest that fluoxetine treatment targets steps of early colon carcinogenesis. This confirms its protective potential, explaining at least partially the lower colon cancer risk under antidepressant therapy.

show abstract

Altered gene expression and miRNA expression associated with cancerous IEC-6 cell transformed by MNNG

Cited by 12 publications

References 37 publications

Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model

Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model

Molecular mechanisms for inhibition of colon cancer cells by combined epigenetic-modulating epigallocatechin gallate and sodium butyrate

Correction: Antiproliferative Effects of Fluoxetine on Colon Cancer Cells and in a Colonic Carcinogen Mouse Model

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