Direct Binding of Bcl‑2 Family Proteins by Quercetin Triggers Its Pro-Apoptotic Activity

• Published in: ACS chemical biology Vol. 9; no. 12; pp. 2737 - 2741
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 19.12.2014
• Subjects: Antineoplastic Agents, Phytogenic - chemistry; Antineoplastic Agents, Phytogenic - metabolism; Apoptosis - drug effects; Apoptosis - genetics; bcl-X Protein - chemistry; bcl-X Protein - genetics; bcl-X Protein - metabolism; Escherichia coli - genetics; Escherichia coli - metabolism; Gene Expression; Gene Expression Regulation, Neoplastic; Humans; Jurkat Cells; Molecular Docking Simulation; Protein Binding; Protein Interaction Domains and Motifs; Proto-Oncogene Proteins c-bcl-2 - chemistry; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Quercetin - chemistry; Quercetin - metabolism; Recombinant Proteins - chemistry; Recombinant Proteins - genetics; Recombinant Proteins - metabolism; Signal Transduction
• ISSN: 1554-8929; 1554-8937; 1554-8937
• DOI: 10.1021/cb500259e

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.