title: Butein inhibits cell proliferation and induces cell cycle arrest in acute lymphoblastic leukemia via FOXO3a/p27kip1 pathway.
abstract: Acute lymphoblastic leukemia (ALL) is a common hematological malignancy characterized by the uncontrolled proliferation of leukemia cells in children. Discovering and developing effective chemotherapeutic drugs are needed for ALL. In this study, we investigated the anti-leukemic activity of butein and its action mechanisms in ALL. Butein was found to significantly suppress the cellular proliferation of ALL cell lines and primary ALL blasts in a dose-dependent manner. It also induced cell cycle arrest by decreasing the expression of cyclin E and CDK2. We also found that butein promoted nuclear Forkhead Class box O3a (FOXO3a) localization, enhanced the binding of FOXO3a on the p27kip1 gene promoter and then increased the expression of p27kip1. Moreover, we showed that FOXO3a knockdown significantly decreased the proliferation inhibition by butein, whereas overexpression of FOXO3a enhanced the butein-mediated proliferation inhibition. However, overexpression of FOXO3a mutation (C-terminally truncated FOXO3a DNA-binding domain) decreased the proliferation inhibition by butein through decreasing the expression of p27kip1. Our results therefore demonstrate the therapeutic potential of butein for ALL via FOXO3a/p27kip1 pathway.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yan-Lai
authors.initials: YL
authors.lastname: Tang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Li-Bin
authors.initials: LB
authors.lastname: Huang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wen-Hao
authors.initials: WH
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Li-Na
authors.initials: LN
authors.lastname: Wang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Dingbo
authors.initials: D
authors.lastname: Shi
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Jingshu
authors.initials: J
authors.lastname: Wang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.
authors.forename: Ge
authors.initials: G
authors.lastname: Qin
authors.affiliation: Department of Radiation Oncology, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Anchuan
authors.initials: A
authors.lastname: Li
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yan-Ni
authors.initials: YN
authors.lastname: Liang
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Huan-Juan
authors.initials: HJ
authors.lastname: Zhou
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Ke
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.|State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
authors.forename: Wenlin
authors.initials: W
authors.lastname: Huang
authors.affiliation: Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China.|State Key Laboratory of Targeted Drug for Tumors of Guangdong Province, Guangzhou Double Bioproduct Inc., Guangzhou, China.
authors.forename: Wuguo
authors.initials: W
authors.lastname: Deng
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xue-Qun
authors.initials: XQ
authors.lastname: Luo
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D047188:Chalcones / Q000494:pharmacology*; D002648:Child; D002675:Child, Preschool; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D005260:Female; D000071316:Forkhead Box Protein O3 / Q000378:metabolism*; D006801:Humans; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C436291:CDKN1B protein, human; D047188:Chalcones; C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D050760:Cyclin-Dependent Kinase Inhibitor p27; C040918:butein
keywords: FOXO3a; acute lymphoblastic leukemia; butein; p27kip1