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Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells
BACKGROUND: DNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinoki...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327573/ https://www.ncbi.nlm.nih.gov/pubmed/28241740 http://dx.doi.org/10.1186/s12860-017-0130-3 |
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author | Seo, Jung Seon Choi, Young Ha Moon, Ji Wook Kim, Hyeon Soo Park, Sun-Hwa |
author_facet | Seo, Jung Seon Choi, Young Ha Moon, Ji Wook Kim, Hyeon Soo Park, Sun-Hwa |
author_sort | Seo, Jung Seon |
collection | PubMed |
description | BACKGROUND: DNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinokitiol and DNA methylation is not clear. The aim of our study was to explore whether hinokitiol has an inhibitory ability on the DNA methylation in colon cancer cells. RESULTS: MTT data showed that hinokitiol had higher sensitivity in colon cancer cells, HCT-116 and SW480, than in normal colon cells, CCD18Co. Hinokitiol reduced DNA methyltransferase 1 (DNMT1) and ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression in HCT-116 cells. In addition, the expression of ten-eleven translocation protein 1 (TET1), a known DNA demethylation initiator, was increased by hinokitiol treatment. ELISA and FACS data showed that hinokitiol increased the 5-hydroxymethylcytosine (5hmC) level in the both colon cancer cells, but 5-methylcytosine (5mC) level was not changed. Furthermore, hinokitiol significantly restored mRNA expression of O(6)-methylguanine DNA methyltransferase (MGMT), carbohydrate sulfotransferase 10 (CHST10), and B-cell translocation gene 4 (BTG4) concomitant with reduction of methylation status in HCT-116 cells. CONCLUSIONS: These results indicate that hinokitiol may exert DNA demethylation by inhibiting the expression of DNMT1 and UHRF1 in colon cancer cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-017-0130-3) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-5327573 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-53275732017-03-03 Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells Seo, Jung Seon Choi, Young Ha Moon, Ji Wook Kim, Hyeon Soo Park, Sun-Hwa BMC Cell Biol Research Article BACKGROUND: DNA hypermethylation is a key epigenetic mechanism for the silencing of many genes in cancer. Hinokitiol, a tropolone-related natural compound, is known to induce apoptosis and cell cycle arrest and has anti-inflammatory and anti-tumor activities. However, the relationship between hinokitiol and DNA methylation is not clear. The aim of our study was to explore whether hinokitiol has an inhibitory ability on the DNA methylation in colon cancer cells. RESULTS: MTT data showed that hinokitiol had higher sensitivity in colon cancer cells, HCT-116 and SW480, than in normal colon cells, CCD18Co. Hinokitiol reduced DNA methyltransferase 1 (DNMT1) and ubiquitin-like plant homeodomain and RING finger domain 1 (UHRF1) expression in HCT-116 cells. In addition, the expression of ten-eleven translocation protein 1 (TET1), a known DNA demethylation initiator, was increased by hinokitiol treatment. ELISA and FACS data showed that hinokitiol increased the 5-hydroxymethylcytosine (5hmC) level in the both colon cancer cells, but 5-methylcytosine (5mC) level was not changed. Furthermore, hinokitiol significantly restored mRNA expression of O(6)-methylguanine DNA methyltransferase (MGMT), carbohydrate sulfotransferase 10 (CHST10), and B-cell translocation gene 4 (BTG4) concomitant with reduction of methylation status in HCT-116 cells. CONCLUSIONS: These results indicate that hinokitiol may exert DNA demethylation by inhibiting the expression of DNMT1 and UHRF1 in colon cancer cells. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12860-017-0130-3) contains supplementary material, which is available to authorized users. BioMed Central 2017-02-27 /pmc/articles/PMC5327573/ /pubmed/28241740 http://dx.doi.org/10.1186/s12860-017-0130-3 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Seo, Jung Seon Choi, Young Ha Moon, Ji Wook Kim, Hyeon Soo Park, Sun-Hwa Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells |
title | Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells |
title_full | Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells |
title_fullStr | Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells |
title_full_unstemmed | Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells |
title_short | Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells |
title_sort | hinokitiol induces dna demethylation via dnmt1 and uhrf1 inhibition in colon cancer cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5327573/ https://www.ncbi.nlm.nih.gov/pubmed/28241740 http://dx.doi.org/10.1186/s12860-017-0130-3 |
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