Direct Binding of Bcl-2 Family Proteins by Quercetin Triggers Its Pro-Apoptotic Activity
Alexandra Primikyri, Μaria V. Chatziathanasiadou, Evdoxia Karali, Eleftherios Kostaras, Michalis D. Mantzaris, Eleftheria ChR. Hatzimichael, Jae‐Sun Shin, Seung‐Wook Chi, Evangelos C. Briasoulis, Evangelos Kolettas, Ioannis P. Gerothanassis, Andreas G. Tzakos · ACS Chemical Biology · 2014
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.