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

Sonam Sinha, Samriddhi Shukla, Sajid Khan, Trygve O. Tollefsbol, Syed M. Meeran

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

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 p21CIP1/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.

Original languageEnglish (US)
Pages (from-to)102-114
Number of pages13
JournalMolecular and Cellular Endocrinology
Volume406
DOIs
StatePublished - May 5 2015
Externally publishedYes

Keywords

  • Breast cancer
  • Epigenetics
  • Estrogen receptor
  • Green tea
  • Sulforaphane
  • Tumor suppressor genes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Fingerprint

Dive into the research topics of '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'. Together they form a unique fingerprint.

Cite this