title: Direct binding of Bcl-2 family proteins by quercetin triggers its pro-apoptotic activity.
abstract: 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.
authors.affiliation: 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.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Primikyri
authors.forename: Maria V
authors.initials: MV
authors.lastname: Chatziathanasiadou
authors.forename: Evdoxia
authors.initials: E
authors.lastname: Karali
authors.forename: Eleftherios
authors.initials: E
authors.lastname: Kostaras
authors.forename: Michalis D
authors.initials: MD
authors.lastname: Mantzaris
authors.forename: Eleftheria
authors.initials: E
authors.lastname: Hatzimichael
authors.forename: Jae-Sun
authors.initials: JS
authors.lastname: Shin
authors.forename: Seung-Wook
authors.initials: SW
authors.lastname: Chi
authors.forename: Evangelos
authors.initials: E
authors.lastname: Briasoulis
authors.forename: Evangelos
authors.initials: E
authors.lastname: Kolettas
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Gerothanassis
authors.forename: Andreas G
authors.initials: AG
authors.lastname: Tzakos
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry* / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D019169:Jurkat Cells; D062105:Molecular Docking Simulation; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011794:Quercetin / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051020:bcl-X Protein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C000595707:BCL2 protein, human; C494811:BCL2L1 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D051020:bcl-X Protein; D011794:Quercetin