DAXX-inducing phytoestrogens inhibit ER+ tumor initiating cells and delay tumor development

• DOI: 10.1038/s41523-020-00178-5
• Publication Date: 2020-08-14T12:27:09Z
• Authors: Daniel S. Peiffer; Emily Ma; Debra Wyatt; Kathy S. Albain; Clodia Osipo
• Keywords: Death-associated protein 6

Abstract Recurrence of estrogen receptor (ER)-positive breast tumors despite curative-intent adjuvant therapy is thought to be due enrichment tumor initiating cells (TIC) during endocrine (ET). Recently, it was identified that by antagonizing the ER, ET promotes rapid degradation death-associated factor 6 (DAXX) protein, which necessary and sufficient potently inhibit TICs. Thus, goal current study identify a DAXX-inducing agent TICs prevent proliferation tumor. Phytoestrogens (naringenin, resveratrol, genistein, apigenin, quercetin) were screened for DAXX protein expression, anti-TIC anti-proliferative efficacy in vitro vivo. Specific phytoestrogens tested assess selectivity towards ERα and/or ERβ. Results showed induced expression inhibited survival from ER+ MCF-7 T47D cells. Only naringenin, quercetin did not stimulate total cell proliferation. Naringenin, but vivo DAXX-dependent manner. Naringenin-induced inhibition seemed more selective ERβ while resveratrol through ERα. Naringenin or rate initiation growth These results suggest therapeutic approach using phytoestrogen induce could within delay initiation. Therefore, DAXX-promoting should explored prevention progression advanced disease relapse setting.