Department of Food Science , University of Guelph , 50 Stone Road E , Guelph , Ontario , Canada , N1G 2W1.
School of Pharmacy , University of Waterloo , 10A Victoria Street S , Kitchener , Ontario , Canada , N2G 1C5.
Mol Pharm. 2018 Mar 5;15(3):1353-1360. doi: 10.1021/acs.molpharmaceut.7b01151. Epub 2018 Feb 7.
Acute myeloid leukemia is an aggressive disease with limited and nonselective therapeutic options. This study explored the bioactivity and cell death inducing mechanism of diosmetin, a novel compound identified in a nutraceutical screen to impart selective anti-AML activity. Diosmetin, a citrus flavone, induced apoptosis characterized by increases in caspases 8 and 3/7 and the death inducing cytokine TNFα. In fact, through protein and mRNA expression analysis, activity was shown to be dependent on expression of estrogen receptor (ER) β. Treatment with diosmetin also delayed tumor growth in AML mouse xenografts. In summary, these studies highlight diosmetin as a novel therapeutic that induces apoptosis through estrogen receptor β.
急性髓系白血病是一种侵袭性疾病，治疗方法有限且无选择性。本研究探讨了一种新型化合物地奥司明的生物活性和诱导细胞死亡的机制，该化合物是在营养保健品筛选中发现的，具有选择性的抗急性髓系白血病活性。地奥司明是一种柑橘类黄酮，可诱导细胞凋亡，其特征是半胱天冬酶 8 和 3/7 以及诱导细胞死亡的细胞因子 TNFα 增加。事实上，通过蛋白质和 mRNA 表达分析，活性依赖于雌激素受体 (ER) β 的表达。地奥司明治疗还延迟了 AML 小鼠异种移植物中的肿瘤生长。总之，这些研究强调了地奥司明作为一种通过雌激素受体 β 诱导细胞凋亡的新型治疗药物的重要性。
