Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice
Chronic inflammation is an underlying risk factor for colon cancer. Tumor necrosis factor alpha (TNF-α) plays a critical role in the development of inflammation-induced colon cancer in a mouse model. S-adenosylmethionine (SAMe) and its metabolite methylthioadenosine (MTA) can inhibit lipopolysacchar...
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Oxford University Press
2012
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| On-line přístup: | https://ncbi.nlm.nih.gov/pmc/articles/PMC3279046/ https://ncbi.nlm.nih.gov/pubmed/22159228 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/carcin/bgr295 |
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pubmed-32790462013-02-01 Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice Li, Tony W.H. Yang, Heping Peng, Hui Xia, Meng Mato, José M. Lu, Shelly C. Carcinogenesis Inflammation, Microenvironment and Prevention Chronic inflammation is an underlying risk factor for colon cancer. Tumor necrosis factor alpha (TNF-α) plays a critical role in the development of inflammation-induced colon cancer in a mouse model. S-adenosylmethionine (SAMe) and its metabolite methylthioadenosine (MTA) can inhibit lipopolysaccharide-induced TNF-α expression in macrophages. The aim of this work was to examine whether SAMe and MTA are effective in preventing inflammation-induced colon cancer and if so identify signaling pathways affected. Balb/c mice were treated with azoxymethane (AOM) and dextran sulfate sodium to induce colon cancer. Two days after AOM treatment, mice were divided into three groups: vehicle control, SAMe or MTA. Tumor load, histology, immunohistochemistry, gene and protein expression were determined. SAMe and MTA treatment reduced tumor load by ∼40%. Both treatments raised SAMe and MTA levels but MTA also raised S-adenosylhomocysteine levels. MTA treatment prevented the induction of many genes known to play pathogenetic roles in this model except for TNF-α and inducible nitric oxide synthase (iNOS). SAMe also had no effect on TNF-α or iNOS and was less inhibitory than MTA on the other genes. In vivo, both treatments induced apoptosis but inhibited proliferation, β-catenin, nuclear factor kappa B activation and interleukin (IL) 6 signaling. Effect of SAMe and MTA on IL-6 signaling was examined using Colo 205 colon cancer cells. In these cells, SAMe and MTA inhibited IL-6-induced IL-10 expression. MTA also inhibited IL-10 transcription and signal transducer and activator of transcription 3 activation. In conclusion, SAMe and MTA reduced inflammation-induced colon cancer and inhibited several pathways important in colon carcinogenesis. Oxford University Press 2012-02 2011-12-09 /pmc/articles/PMC3279046/ /pubmed/22159228 http://dx.doi.org/10.1093/carcin/bgr295 Text en © The Author 2011. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com |
| institution |
US NLM |
| collection |
PubMed Central |
| language |
Inglês |
| format |
Artigo |
| topic |
Inflammation, Microenvironment and Prevention |
| spellingShingle |
Inflammation, Microenvironment and Prevention Li, Tony W.H. Yang, Heping Peng, Hui Xia, Meng Mato, José M. Lu, Shelly C. Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice |
| description |
Chronic inflammation is an underlying risk factor for colon cancer. Tumor necrosis factor alpha (TNF-α) plays a critical role in the development of inflammation-induced colon cancer in a mouse model. S-adenosylmethionine (SAMe) and its metabolite methylthioadenosine (MTA) can inhibit lipopolysaccharide-induced TNF-α expression in macrophages. The aim of this work was to examine whether SAMe and MTA are effective in preventing inflammation-induced colon cancer and if so identify signaling pathways affected. Balb/c mice were treated with azoxymethane (AOM) and dextran sulfate sodium to induce colon cancer. Two days after AOM treatment, mice were divided into three groups: vehicle control, SAMe or MTA. Tumor load, histology, immunohistochemistry, gene and protein expression were determined. SAMe and MTA treatment reduced tumor load by ∼40%. Both treatments raised SAMe and MTA levels but MTA also raised S-adenosylhomocysteine levels. MTA treatment prevented the induction of many genes known to play pathogenetic roles in this model except for TNF-α and inducible nitric oxide synthase (iNOS). SAMe also had no effect on TNF-α or iNOS and was less inhibitory than MTA on the other genes. In vivo, both treatments induced apoptosis but inhibited proliferation, β-catenin, nuclear factor kappa B activation and interleukin (IL) 6 signaling. Effect of SAMe and MTA on IL-6 signaling was examined using Colo 205 colon cancer cells. In these cells, SAMe and MTA inhibited IL-6-induced IL-10 expression. MTA also inhibited IL-10 transcription and signal transducer and activator of transcription 3 activation. In conclusion, SAMe and MTA reduced inflammation-induced colon cancer and inhibited several pathways important in colon carcinogenesis. |
| author |
Li, Tony W.H. Yang, Heping Peng, Hui Xia, Meng Mato, José M. Lu, Shelly C. |
| author_facet |
Li, Tony W.H. Yang, Heping Peng, Hui Xia, Meng Mato, José M. Lu, Shelly C. |
| author_sort |
Li, Tony W.H. |
| title |
Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice |
| title_short |
Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice |
| title_full |
Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice |
| title_fullStr |
Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice |
| title_full_unstemmed |
Effects of S-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice |
| title_sort |
effects of s-adenosylmethionine and methylthioadenosine on inflammation-induced colon cancer in mice |
| publisher |
Oxford University Press |
| publishDate |
2012 |
| url |
https://ncbi.nlm.nih.gov/pmc/articles/PMC3279046/ https://ncbi.nlm.nih.gov/pubmed/22159228 https://ncbi.nlm.nih.govhttp://dx.doi.org/10.1093/carcin/bgr295 |
| _version_ |
1757087324193161216 |