Estrogen Receptor β Is a Novel Target in Acute Myeloid Leukemia
- PMID: 28835383
- DOI: 10.1158/1535-7163.MCT-17-0292
Estrogen Receptor β Is a Novel Target in Acute Myeloid Leukemia
Abstract
Acute myeloid leukemia (AML) is a devastating disease characterized by poor patient outcome and suboptimal chemotherapeutics. Here, a high-throughput screen identified diosmetin, a citrus flavonoid, with anti-AML activity. Diosmetin imparted selective toxicity against leukemia and leukemia stem cells in vitro and in vivo with no effect on normal hematopoietic stem cells. Mechanistically, we demonstrated that diosmetin targets estrogen receptor (ER) β. ERβ expression conferred cell sensitivity, as patient-derived AML cells with high levels of ERβ were sensitive, whereas cells with low ERβ were insensitive to diosmetin. Knockdown of ERβ confirmed resistance, whereas overexpression enhanced sensitivity to diosmetin, which was demonstrated to be mediated by reactive oxygen species signaling. In summary, these studies highlight targeting of ERβ with diosmetin as a potential novel therapeutic strategy for the treatment of AML. Mol Cancer Ther; 16(11); 2618-26. ©2017 AACR.
©2017 American Association for Cancer Research.
Similar articles
-
Diosmetin Induces Apoptosis of Acute Myeloid Leukemia Cells.Mol Pharm. 2018 Mar 5;15(3):1353-1360. doi: 10.1021/acs.molpharmaceut.7b01151. Epub 2018 Feb 7. Mol Pharm. 2018. PMID: 29412683
-
Disulfiram/copper selectively eradicates AML leukemia stem cells in vitro and in vivo by simultaneous induction of ROS-JNK and inhibition of NF-κB and Nrf2.Cell Death Dis. 2017 May 18;8(5):e2797. doi: 10.1038/cddis.2017.176. Cell Death Dis. 2017. PMID: 28518151 Free PMC article.
-
A New Strategy to Target Acute Myeloid Leukemia Stem and Progenitor Cells Using Chidamide, a Histone Deacetylase Inhibitor.Curr Cancer Drug Targets. 2015;15(6):493-503. doi: 10.2174/156800961506150805153230. Curr Cancer Drug Targets. 2015. PMID: 26282548
-
Identification of TIM-3 as a Leukemic Stem Cell Surface Molecule in Primary Acute Myeloid Leukemia.Oncology. 2015;89 Suppl 1:28-32. doi: 10.1159/000431062. Epub 2015 Nov 10. Oncology. 2015. PMID: 26551150 Review.
-
Estrogen Receptors Alpha and Beta in Acute Myeloid Leukemia.Cancers (Basel). 2020 Apr 8;12(4):907. doi: 10.3390/cancers12040907. Cancers (Basel). 2020. PMID: 32276421 Free PMC article. Review.
Cited by
-
Targeted activation of GPER enhances the efficacy of venetoclax by boosting leukemic pyroptosis and CD8+ T cell immune function in acute myeloid leukemia.Cell Death Dis. 2022 Oct 31;13(10):915. doi: 10.1038/s41419-022-05357-9. Cell Death Dis. 2022. PMID: 36316313 Free PMC article.
-
Knockdown of BNIP3L or SQSTM1 alters cellular response to mitochondria target drugs.Autophagy. 2019 May;15(5):900-907. doi: 10.1080/15548627.2018.1558002. Epub 2019 Jan 9. Autophagy. 2019. PMID: 30563411 Free PMC article.
-
Long-term cardiac-specific mortality among 44,292 acute myeloid leukemia patients treated with chemotherapy: a population-based analysis.J Cancer. 2019 Oct 15;10(24):6161-6169. doi: 10.7150/jca.36948. eCollection 2019. J Cancer. 2019. PMID: 31762826 Free PMC article.
-
A Prognostic Model for Acute Myeloid Leukemia Based on IL-2/STAT5 Pathway-Related Genes.Front Oncol. 2022 Feb 2;12:785899. doi: 10.3389/fonc.2022.785899. eCollection 2022. Front Oncol. 2022. PMID: 35186733 Free PMC article.
-
Anticancer efficacy of 3-(4-isopropyl) benzylidene-8-ethoxy, 6-methyl, chroman-4-one (SBL-060), a novel, dual, estrogen receptor-Akt kinase inhibitor in acute myeloid leukemia cells.Oncol Res. 2022 Aug 1;29(3):149-157. doi: 10.32604/or.2022.03539. eCollection 2021. Oncol Res. 2022. PMID: 37304671 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
