Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines
Meeran SM, Patel SN, Tollefsbol TO
PloS one · 258 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- Cells or lab samples
- Main outcome
- Mechanisms only
Who paid for it
- Funding
- Independent funding
- Government
- National Cancer Institute
- Government
- NCI NIH HHS
- Grants
- National Cancer Institute (R01 CA129415); National Cancer Institute (CA129415)
Based on 2 listed funder(s).
Publication
- Published
- 2010-07-06 · PLoS One · vol. 5 · issue 7 · p. e11457
- Publisher
- Public Library of Science
- Cited
- 370 citations · more than 99% of similar papers · 10.6× the field average
- Impact
- Top 10% most cited in its field
- References
- 44 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · Epigenetics and DNA Methylation · Glutathione Transferases and Polymorphisms
- Keywords
- Telomerase reverse transcriptase, Cancer research, Telomerase, Histone deacetylase, Chromatin immunoprecipitation, Biology, CTCF, Molecular biology, Chemistry, Histone, Gene expression, Genetics, Promoter
- MeSH
- cell line, tumor, humans, breast neoplasms, thiocyanates, isothiocyanates, sulfoxides, telomerase, repressor proteins, rna, small interfering, blotting, western, electrophoresis, polyacrylamide gel, chromatin immunoprecipitation, reverse transcriptase polymerase chain reaction, apoptosis, cell proliferation, dna methylation, gene expression regulation, neoplastic, acetylation, female, promoter regions, genetic, dna (cytosine-5-)-methyltransferase 1, ccctc-binding factor, dna (cytosine-5-)-methyltransferases, dna methyltransferase 3a
3 authors
From US
- Syed Musthapa MeeranUniversity of Alabama at Birmingham
- Shweta N. PatelUniversity of Alabama at Birmingham
- Trygve O. Tollefsbol · correspondingUniversity of Alabama at Birmingham
Abstract
Background
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is a common dietary component that has histone deacetylase inhibition activity and exciting potential in cancer prevention. The mechanisms by which SFN imparts its chemopreventive properties are of considerable interest and little is known of its preventive potential for breast cancer.
Principal findings
We found that SFN significantly inhibits the viability and proliferation of breast cancer cells in vitro while it has negligible effects on normal breast cells. Inhibition of telomerase has received considerable attention because of its high expression in cancer cells and extremely low level of expression in normal cells. SFN treatment dose- and time-dependently inhibited human telomerase reverse transcriptase (hTERT), the catalytic regulatory subunit of telomerase, in both MCF-7 and MDA-MB-231 human breast cancer cells. DNA methyltransferases (DNMTs), especially DNMT1 and DNMT3a, were also decreased in SFN-treated breast cancer cells suggesting that SFN may repress hTERT by impacting epigenetic pathways. Down-regulation of DNMTs in response to SFN induced site-specific CpG demethylation occurring primarily in the first exon of the hTERT gene thereby facilitating CTCF binding associated with hTERT repression. Chromatin immunoprecipitation (ChIP) analysis of the hTERT promoter revealed that SFN increased the level of active chromatin markers acetyl-H3, acetyl-H3K9 and acetyl-H4, whereas the trimethyl-H3K9 and trimethyl-H3K27 inactive chromatin markers were decreased in a dose-dependent manner. SFN-induced hyperacetylation facilitated the binding of many hTERT repressor proteins such as MAD1 and CTCF to the hTERT regulatory region. Depletion of CTCF using siRNA reduced the SFN-induced down-regulation of hTERT mRNA transcription in these breast cancer cells. In addition, down-regulation of hTERT expression facilitated the induction of cellular apoptosis in human breast cancer cells.
Significance
Collectively, our results provide novel insights into SFN-mediated epigenetic down-regulation of telomerase in breast cancer prevention and may open new avenues for approaches to SFN-mediated cancer prevention.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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