title: Anthocyanins from roselle extract arrest cell cycle G2/M phase transition via ATM/Chk pathway in p53-deficient leukemia HL-60 cells.
abstract: Cell cycle regulation is an important issue in cancer therapy. Delphinidin and cyanidin are two major anthocyanins of the roselle plant (Hibiscus sabdariffa). In the present study, we investigated the effect of Hibiscus anthocyanins (HAs) on cell cycle arrest in human leukemia cell line HL-60 and the analyzed the underlying molecular mechanisms. HAs extracted from roselle calyces (purity 90%) markedly induced G2/M arrest evaluated with flow cytometry analysis. Western blot analyses revealed that HAs (0.1-0.7 mg mL-1) induced G2/M arrest via increasing Tyr15 phosphorylation of Cdc2, and inducing Cdk inhibitors p27 and p21. HAs also induced phosphorylation of upstream signals related to G2/M arrest such as phosphorylation of Cdc25C tyrosine phosphatase at Ser216, increasing the binding of pCdc25C with 14-3-3 protein. HAs-induced phosphorylation of Cdc25C could be activated by ATM checkpoint kinases, Chk1, and Chk2. We first time confirmed that ATM-Chk1/2-Cdc25C pathway as a critical mechanism for G2/M arrest in HAs-induced leukemia cell cycle arrest, indicating that this compound could be a promising anticancer candidate or chemopreventive agents for further investigation. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1290-1304, 2017.
authors.affiliation: Superintendent Office, Antai Medical Care Cooperation, Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan.
authors.forename: Tsung-Chang
authors.initials: TC
authors.lastname: Tsai
authors.affiliation: Department of Biochemistry, School of Medicine, Chung Shan Medical University, Taichung, Taiwan.|Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Hui-Pei
authors.initials: HP
authors.lastname: Huang
authors.affiliation: Institute of Biochemistry, Microbiology and Immunology, Medical College, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Kai-Ting
authors.initials: KT
authors.lastname: Chang
authors.affiliation: Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Biochemistry, Microbiology and Immunology, Medical College, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Chau-Jong
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan.|Institute of Biochemistry, Microbiology and Immunology, Medical College, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Yun-Ching
authors.initials: YC
authors.lastname: Chang
mesh_terms: D048948:14-3-3 Proteins / Q000378:metabolism; D000872:Anthocyanins / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D000071877:Checkpoint Kinase 1 / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000378:metabolism; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects*; D018922:HL-60 Cells; D031584:Hibiscus / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D007938:Leukemia / Q000378:metabolism / Q000473:pathology; D059566:M Phase Cell Cycle Checkpoints / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D010936:Plant Extracts / Q000737:chemistry; D015398:Signal Transduction / Q000187:drug effects*; D016159:Tumor Suppressor Protein p53 / Q000172:deficiency / Q000235:genetics*; D020687:cdc25 Phosphatases / Q000378:metabolism
chemical_list: D048948:14-3-3 Proteins; D000872:Anthocyanins; D010936:Plant Extracts; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D064447:Checkpoint Kinase 2; D064007:Ataxia Telangiectasia Mutated Proteins; D000071877:Checkpoint Kinase 1; D016203:CDC2 Protein Kinase; D020687:cdc25 Phosphatases
keywords: HL-60 cells; Hibiscus sabdariffa Linnaeus; anthocyanins; cell cycle arrest