McGill Colin M, Brown Timothy J, Fisher Lindsey N, Gustafson Sally J, Dunlap Kriya L, Beck Adam J, Toran Paul T, Claxton David F, Barth Brian M
Department of Chemistry, University of Alaska-Anchorage, Anchorage, AK 99508 USA.
Department of Medicine, Division of Hematology and Oncology, Penn State Hershey Cancer Institute, Penn State College of Medicine, Hershey, PA 17033 USA.
Int J Biopharm Sci. 2018;1(1). doi: 10.31021/ijbs.20181106. Epub 2018 Jan 31.
Acute myeloid leukemia (AML) is an aggressive hematological malignancy with limited treatment options. Inflammation is often a contributing factor to the development and progression of AML, and related diseases, and can potentiate therapy failure. Previously, we had identified anti-inflammatory roles and anti-AML efficacy for blueberry extracts. The present study extended these observations to determine that the polyphenol quercetin inhibited neutral sphingomyelinase (N-SMase) activity and exerted anti-AML efficacy. Moreover, quercetin was shown to exert combinatorial anti-AML efficacy with nanoliposomal ceramide. Overall, this demonstrated that quercetin could block the pro-inflammatory actions of N-SMase and augment the efficacy of anti-AML therapeutics, including ceramide-based therapeutics.
急性髓系白血病（AML）是一种侵袭性血液系统恶性肿瘤，治疗选择有限。炎症往往是AML及其相关疾病发生和进展的一个促成因素，并且会加剧治疗失败。此前，我们已确定蓝莓提取物具有抗炎作用和抗AML疗效。本研究扩展了这些观察结果，以确定多酚槲皮素可抑制中性鞘磷脂酶（N-SMase）活性并发挥抗AML疗效。此外，槲皮素还显示出与纳米脂质体神经酰胺联合发挥抗AML疗效。总体而言，这表明槲皮素可阻断N-SMase的促炎作用，并增强包括基于神经酰胺的疗法在内的抗AML治疗药物的疗效。
