title: Quercetin-induced apoptosis of HL-60 cells by reducing PI3K/Akt.
abstract: To explore the effect and mechanism of quercetin on proliferation and apoptosis of leukemia cells, and provide a theoretical basis for its clinical application. HL-60 leukemia cell lines was treated with different dose quercetin, the proliferation activity of leukemia cells was assessed by MTT method; the morphological changes of apoptosis of HL-60 cells, including nuclear condensation and DNA fragmentation, were observed by Hoechst 33258 fluorescence staining, the apoptosis rate and caspase 2,3 activation were assessed by flow cytometry, and the cell signal pathway including phosphatidylinositol 3-kinase (PI3K), phosphorylated protein kinase B (pAkt), Bcl-2, Bax were detected by western blotting. Quercetin could significantly decrease the proliferation activity of HL-60 cells through the blockade of G(0)/G(1) phase, and induce the apoptosis of HL-60 cells in a time- and dose-dependent manner. Quercetin caused leukemia cells apoptosis by decreasing the protein expression of PI3K and Bax, the inhibitory phosphorylation of Akt, the decreased levels of Bcl-2 protein and increased activations of caspase-2 and -3, and increased poly(ADP-ribose) polymerase cleavage. Our results indicate that the apoptotic processes caused by quercetin are mediated by the decrease of pAkt and Bcl-2 levels, the increase of Bax level, and the activation of caspase families in HL-60 cells.
authors.affiliation: Hematology Department, Affiliated Dongfeng Hospital, HuBei University of Medicine, Shiyan, 442000, Hubei, People's Republic of China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yuan
authors.forename: Chen
authors.initials: C
authors.lastname: Long
authors.forename: Tang
authors.initials: T
authors.lastname: Junming
authors.forename: Liu
authors.initials: L
authors.lastname: Qihuan
authors.forename: Zhang
authors.initials: Z
authors.lastname: Youshun
authors.forename: Zou
authors.initials: Z
authors.lastname: Chan
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D053143:Caspase 2 / Q000096:biosynthesis / Q000187:drug effects; D053148:Caspase 3 / Q000096:biosynthesis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis*
chemical_list: D051028:bcl-2-Associated X Protein; D011794:Quercetin; D011065:Poly(ADP-ribose) Polymerases; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D053143:Caspase 2; D053148:Caspase 3