Hinokitiol induces DNA demethylation via DNMT1 and UHRF1 inhibition in colon cancer cells

Jung Seon Seo, Young Ha Choi, Ji Wook Moon, Hyeon Soo Kim, Sun-Hwa Park

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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 O6-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.

Original languageEnglish
Article number14
JournalBMC Cell Biology
Volume18
Issue number1
DOIs
Publication statusPublished - 2017 Feb 27

Fingerprint

RING Finger Domains
Methyltransferases
Ubiquitin
Colonic Neoplasms
DNA
HCT116 Cells
DNA Methylation
Tropolone
5-Methylcytosine
beta-thujaplicin
Neoplasm Genes
Gene Silencing
Protein Transport
Cell Cycle Checkpoints
Epigenomics
Methylation
Colon
B-Lymphocytes
Anti-Inflammatory Agents
Enzyme-Linked Immunosorbent Assay

Keywords

  • Anti-tumor activities
  • Colonic neoplasm
  • DNA methylation
  • DNA methylation inhibitor
  • Hinokitiol

ASJC Scopus subject areas

  • Cell Biology

Cite this

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.

In: BMC Cell Biology, Vol. 18, No. 1, 14, 27.02.2017.

Research output: Contribution to journalArticle

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