Primikyri Alexandra, Chatziathanasiadou Maria V, Karali Evdoxia, Kostaras Eleftherios, Mantzaris Michalis D, Hatzimichael Eleftheria, Shin Jae-Sun, Chi Seung-Wook, Briasoulis Evangelos, Kolettas Evangelos, Gerothanassis Ioannis P, Tzakos Andreas G
Section of Organic Chemistry and Biochemistry, Department of Chemistry, ‡Laboratory of Biological Chemistry, School of Medicine, §Cancer Biobank Center, and ⊥Department of Hematology, School of Medicine, ▽Laboratory of Biology, School of Medicine, University of Ioannina , 45110 Ioannina, Greece.
ACS Chem Biol. 2014 Dec 19;9(12):2737-41. doi: 10.1021/cb500259e. Epub 2014 Oct 9.
Bcl-2 family proteins are important regulators of apoptosis and its antiapoptotic members, which are overexpressed in many types of cancer, are of high prognostic significance, establishing them as attractive therapeutic targets. Quercetin, a natural flavonoid, has drawn much attention because it exerts anticancer effects, while sparing normal cells. A multidisciplinary approach has been employed herein, in an effort to reveal its mode of action including dose-response antiproliferative activity and induced apoptosis effect, biochemical and physicochemical assays, and computational calculations. It may be concluded that, quercetin binds directly to the BH3 domain of Bcl-2 and Bcl-xL proteins, thereby inhibiting their activity and promoting cancer cell apoptosis.
Bcl-2家族蛋白是细胞凋亡的重要调节因子，其抗凋亡成员在多种癌症中过度表达，具有很高的预后意义，使其成为有吸引力的治疗靶点。槲皮素是一种天然黄酮类化合物，因其具有抗癌作用且对正常细胞无损害而备受关注。本文采用多学科方法，旨在揭示其作用方式，包括剂量反应抗增殖活性和诱导凋亡效应、生化和物理化学分析以及计算计算。可以得出结论，槲皮素直接与Bcl-2和Bcl-xL蛋白的BH3结构域结合，从而抑制其活性并促进癌细胞凋亡。
