Format

Send to

Choose Destination
Oncol Lett. 2019 Sep;18(3):2639-2647. doi: 10.3892/ol.2019.10569. Epub 2019 Jul 5.

Sulforaphane-induced epigenetic regulation of Nrf2 expression by DNA methyltransferase in human Caco-2 cells.

Author information

1
Medical School, Qi-Lu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
2
Department of of Geriatric Gastroenterology, Qi-Lu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
3
Department of General Practice, Qi-Lu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
4
Jiangxi Medical College of Nanchang University, Nanchang, Jiangxi 330006, P.R. China.
5
Department of General Surgery, Qi-Lu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.

Abstract

The present study aimed to investigate the mechanism underlying sulforaphane-mediated epigenetic regulation of nuclear factor-erythroid derived 2-like 2 (Nrf2) expression in human colon cancer. Proteins were extracted from normal Caco-2 cells using sulforaphane and 5-aza-2'-deoxycytidine (5-Aza) combined with trichostatin A (TSA). The mRNA and protein expression levels and activity of DNA methyltransferase 1 (DNMT1) were determined. Methylation-specific polymerase chain reaction and bisulfite genomic sequencing were also used to measure the methylation levels of CpG sites in the Nrf2 promoter region. Nrf2 expression was measured using reverse transcription-quantitative PCR and western blot analysis. The results demonstrated that sulforaphane did not affect DNMT1 mRNA expression levels. DNMT1 protein expression was inhibited by sulforaphane and 5-Aza co-treatment with TSA. Nrf2 promoter methylation decreased significantly in the sulforaphane group compared with the control group. Nrf2 promoter methylation level in the 5-Aza+TSA group was the lowest among all groups. Nrf2 mRNA levels exhibited significant differences between the sulforaphane-treated and control groups, as well as between the 5-Aza+TSA and control groups, and the sulforaphane-treated and 5-Aza+TSA groups. Nrf2 protein expression was also inhibited by sulforaphane, as well as 5-Aza co-treatment with TSA. The results revealed that sulforaphane may promote demethylation of the Nrf2 promoter region to increase activation of Nrf2, which induces chemoprevention of colon cancer.

KEYWORDS:

chemoprevention; colon tumour; epigenetic regulation; nuclear factor-erythroid derived 2-like 2; sulforaphane

Supplemental Content

Full text links

Icon for PubMed Central
Loading ...
Support Center