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Anthocyanins from roselle extract arrest cell cycle G2/M phase transition via ATM/Chk pathway in p53‐deficient leukemia HL‐60 cells
Author(s) -
Tsai TsungChang,
Huang HuiPei,
Chang KaiTing,
Wang ChauJong,
Chang YunChing
Publication year - 2017
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22324
Subject(s) - cell cycle checkpoint , cyclin dependent kinase 1 , cell cycle , hibiscus sabdariffa , phosphorylation , chemistry , cyclin b1 , microbiology and biotechnology , biology , biochemistry , cancer research , cell , food science
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.