Epigenetic reactivation of p21CIP1/WAF1 and KLOTHO by a combination of bioactive dietary supplements is partially ERα-dependent in ERα-negative human breast cancer cells.
Available treatment strategies against estrogen receptor (ER)-negative breast cancer patients are limited due to their poor response to hormonal therapy. We have shown previously that the combinations of green tea polyphenols (GTPs), a dietary DNA methyltransferase inhibitor, and sulforaphane (SFN), a dietary histone deacetylase inhibitor, reactivate ERα expression in ERα-negative MDA-MB-231 cells. Here, we investigated the functional significance of ERα reactivation in the reactivation of silenced tumor suppressor genes (TSGs) in ERα-negative human breast cancer cells. We found that the treatment of MDA-MB-231 cells with the combinations of GTPs and SFN leads to the reactivation of silenced TSGs such as p21(CIP1/WAF1) and KLOTHO through active chromatin modifications. Further, GTPs- and SFN-mediated reactivation of TSGs was, at least in part, dependent on ERα reactivation in ERα-negative MDA-MB-231 cells. Collectively, our findings suggest that a novel combination of bioactive dietary supplements could further be explored as an effective therapeutic option against hormonal refractory breast cancer.
Laboratory of Cancer Epigenetics, Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031, India.
Sonam
S
Sinha
Laboratory of Cancer Epigenetics, Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031, India.
Samriddhi
S
Shukla
Laboratory of Cancer Epigenetics, Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031, India.
Sajid
S
Khan
Department of Biology, University of Alabama at Birmingham, AL 35294, USA.
Trygve O
TO
Tollefsbol
Laboratory of Cancer Epigenetics, Division of Endocrinology, CSIR-Central Drug Research Institute, Lucknow 226 031, India; Academy of Scientific and Innovative Research (AcSIR), New Delhi, India. Electronic address: s.musthapa@cdri.res.in.
Syed M
SM
Meeran
D001943:Breast Neoplasms / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics*; D019175:DNA Methylation / Q000187:drug effects / Q000235:genetics; D019587:Dietary Supplements; D044127:Epigenesis, Genetic / Q000187:drug effects; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism*; D005260:Female; D005966:Glucuronidase / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D017879:Isothiocyanates / Q000494:pharmacology; D000090265:Klotho Proteins; D059808:Polyphenols / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D013454:Sulfoxides; D013662:Tea / Q000737:chemistry
D002843:Chromatin; D050759:Cyclin-Dependent Kinase Inhibitor p21; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; D006657:Histones; D017879:Isothiocyanates; D059808:Polyphenols; D013454:Sulfoxides; D013662:Tea; D007334:Insulin-Like Growth Factor I; D005966:Glucuronidase; D000090265:Klotho Proteins; C016766:sulforaphane
Breast cancer; Epigenetics; Estrogen receptor; Green tea; Sulforaphane; Tumor suppressor genes