The Effects of Combinatorial Genistein and Sulforaphane in Breast Tumor Inhibition: Role in Epigenetic Regulation
Paul B, Li Y, Tollefsbol TO
International journal of molecular sciences · 71 citations
How it was studied
- Design
- In vitro/mechanistic study (classified by our AI screen)
- Studied in
- People, plus animal or lab work
- Main outcome
- Clinical events such as disease or death
Who paid for it
- Funding
- Independent funding
- Nonprofit
- American Institute for Cancer Research
- Government
- National Institutes of Health
- Government
- National Cancer Institute
- Government
- National Center for Complementary and Integrative Health
- Government
- NCI NIH HHS
- Government
- NCCIH NIH HHS
- Grants
- National Cancer Institute (R01 CA204346); National Cancer Institute (R01 CA178441); American Institute for Cancer Research (AICR316184); National Center for Complementary and Integrative Health (K01AT009373); National Institutes of Health (K01AT009373); National Institutes of Health (R01 CA204346); National Institutes of Health (R01 CA178441); National Institutes of Health (R01 CA178441; R01 CA204346; K01AT009373)
Based on 6 listed funder(s) and full-text disclosure statement.
Publication
- Published
- 2018-06-13 · Int J Mol Sci · vol. 19 · issue 6 · p. 1754
- Publisher
- Multidisciplinary Digital Publishing Institute
- Cited
- 105 citations · more than 95% of similar papers · 3.9× the field average
- Impact
- Top 10% most cited in its field
- References
- 70 works
- Access
- Open access (journal) · CC-BY
- Research areas
- Genomics, phytochemicals, and oxidative stress · Epigenetics and DNA Methylation · Family Support in Illness
- Keywords
- Sulforaphane, Genistein, Epigenetics, Histone deacetylase, Chemistry, Cancer research, Cruciferous vegetables, Epigenetic therapy, Histone deacetylase 2, Apoptosis, Cancer, Pharmacology, Biology, DNA methylation, Biochemistry, Histone, Endocrinology, Gene expression, Genetics, DNA
- MeSH
- animals, humans, mice, mammary neoplasms, animal, isothiocyanates, sulfoxides, genistein, histone deacetylases, antineoplastic agents, antineoplastic combined chemotherapy protocols, epigenesis, genetic, drug synergism, aged, female, kruppel-like transcription factors, histone deacetylase 2, histone deacetylase inhibitors, mcf-7 cells, kruppel-like factor 4, histone deacetylase 3
3 authors
From US
- Bidisha PaulUniversity of Alabama at Birmingham
- Yuanyuan LiUniversity of Alabama at Birmingham
- Trygve O. Tollefsbol · correspondingUniversity of Alabama at Birmingham
Abstract
Dietary compounds that possess the properties of altering epigenetic processes are gaining popularity as targets for cancer prevention studies. These compounds when administered at optimal concentrations and especially in combination can have enhanced effects in cancer prevention or therapy. It is important to study the interaction of two or more compounds in order to assess their role in enhancing prevention. Genistein (GEN), found in soy, has been extensively studied for its role as an epigenetic modifier especially as a DNA methyltransferase (DNMT) inhibitor and sulforaphane (SFN), found in cruciferous vegetables, is known as a histone deacetylase (HDAC) inhibitor. However, very little is known about the effects of these two compounds in conjunction in breast cancer prevention or therapy. In our current study, we determined that, at certain doses, the compounds have synergistic effects in decreasing cellular viability of breast cancer cell lines. Our results indicate that the combination of GEN and SFN is much more effective than their single doses in increasing the rate of apoptosis and lowering the colony forming potential of these cells. We determined that these compounds inhibit cell cycle progression to G2 phase in MDA-MB-231 and G1 phase in MCF-7 breast cancer cell lines. Additionally, we determined that the combination is effective as an HDAC and histone methyltransferase (HMT) inhibitor. Furthermore, we demonstrated that this combination downregulates the levels of HDAC2 and HDAC3 both at the mRNA and protein levels. We also found that these compounds have the potential to downregulate KLF4 levels, which plays an important role in stem cell formation. The combination of GEN and SFN is also effective in downregulating hTERT levels, which is known to be activated when KLF4 binds to its promoter region. Our hypothesis is further strengthened by in vivo studies, where the combination is administered to transgenic mice in the form of genistein and SFN-enriched broccoli sprouts. We have demonstrated that the combination is more effective in preventing or treating mammary cancer via extending tumor latency and reducing tumor volumes/sizes than either of these dietary components administered alone. These results are consistent with our in vitro study suggesting potential preventive and therapeutic effects of this novel dietary combinatorial approach against breast cancer.
Abstract via Europe PMC. Copyright remains with the authors or publisher (CC BY).
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