Effects of sulforaphane and 3,3'-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells
Wong CP, Hsu A, Buchanan A, Palomera-Sanchez Z, Beaver LM, Houseman EA, Williams DE, Dashwood RH, Ho E
PloS one · 76 citations
Review labels
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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
- University or hospital
- Oregon State University
- Government
- National Institutes of Health
- Government
- National Cancer Institute
- Government
- National Institute of General Medical Sciences
- Government
- National Institute of Environmental Health Sciences
- Government
- NCI NIH HHS
- Government
- NIGMS NIH HHS
- Government
- NIEHS NIH HHS
- Grants
- National Cancer Institute (R01 CA-122906); National Cancer Institute (CA-80176); Oregon State University (P30 ES00210); National Institute of Environmental Health Sciences (ES-00-210); National Cancer Institute (R29 CA065525); National Institute of General Medical Sciences (R01 GM104977); National Institute of Environmental Health Sciences (P30ES000210); National Institute of Environmental Health Sciences (#P30-ES00210); National Cancer Institute (CA 90890); National Cancer Institute (CA-65525); National Cancer Institute (R01 CA080176); National Cancer Institute (R01 CA065525); National Cancer Institute (P01 CA090890); National Cancer Institute (R01 CA122959); National Cancer Institute (CA122959); National Cancer Institute (CA122906); National Institutes of Health (CA-65525); National Institutes of Health (CA-80176); National Institutes of Health (CA-90890); National Institutes of Health (CA122906); National Institutes of Health (#ES00210); National Institutes of Health (CA122959); National Institutes of Health (R01GM104977); National Institutes of Health (P30ES00210)
Based on 8 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2014-01-22 · PLoS One · vol. 9 · issue 1 · p. e86787
- Publisher
- Public Library of Science
- Cited
- 123 citations · more than 98% of similar papers · 7.1× the field average
- Impact
- Top 10% most cited in its field
- References
- 50 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · Epigenetics and DNA Methylation · Polyamine Metabolism and Applications
- Keywords
- LNCaP, DNA methylation, Prostate cancer, Epigenetics, Cancer research, Methylation, Biology, Carcinogenesis, Cancer, Molecular biology, Gene expression, Gene, Genetics
- MeSH
- prostate, cells, cultured, epithelial cells, humans, prostatic neoplasms, isothiocyanates, sulfoxides, indoles, dna primers, anticarcinogenic agents, analysis of variance, chromatin immunoprecipitation, dna methylation, male, promoter regions, genetic, real-time polymerase chain reaction
9 authors
From US
- Carmen P. WongOregon State University
- Anna J. C. HsuOregon State University
- Alex BuchananOregon State University
- Zoraya Palomera‐SánchezOregon State University
- Laura M. BeaverOregon State University
- Eugene Andres HousemanOregon State University
Abstract
Epigenetic changes, including aberrant DNA methylation, result in altered gene expression and play an important role in carcinogenesis. Phytochemicals such as sulforaphane (SFN) and 3,3'-diindolylmethane (DIM) are promising chemopreventive agents for the treatment of prostate cancer. Both have been shown to induce re-expression of genes, including tumor suppressor genes silenced in cancer cells, via modulation of epigenetic marks including DNA methylation. However, it remained unclear the effects SFN and DIM on DNA methylation at a genomic scale. The goal of this study was to determine the genome-wide effects of SFN and DIM on promoter methylation in normal prostate epithelial cells and prostate cancer cells. Both SFN and DIM treatment decreased DNA methyltransferase expression in normal prostate epithelial cells (PrEC), and androgen-dependent (LnCAP) and androgen-independent (PC3) prostate cancer cells. The effects of SFN and DIM on promoter methylation profiles in normal PrEC, LnCAP and PC3 prostate cancer cells were determined using methyl-DNA immunoprecipitation followed by genome-wide DNA methylation array. We showed widespread changes in promoter methylation patterns, including both increased and decreased methylation, in all three prostate cell lines in response to SFN or DIM treatments. In particular, SFN and DIM altered promoter methylation in distinct sets of genes in PrEC, LnCAP, and PC3 cells, but shared similar gene targets within a single cell line. We further showed that SFN and DIM reversed many of the cancer-associated methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression. Overall, our data suggested that both SFN and DIM are epigenetic modulators that have broad and complex effects on DNA methylation profiles in both normal and cancerous prostate epithelial cells. Results from our study may provide new insights into the epigenetic mechanisms by which SFN and DIM exert their cancer chemopreventive effects.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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