中山醫學大學機構典藏 CSMUIR:Item 310902500/19055
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    題名: Cantharidic acid induces apoptosis of human leukemic HL-60 cells via c-Jun N-terminal kinase-regulated caspase-8/-9/-3 activation pathway
    作者: SC, Wang;JM, Chow;MH, Chien;CW, Lin;HY, Chen;PC, Hsiao;SF, Yang
    貢獻者: 中山醫學大學
    關鍵詞: acute myeloid leukemia;apoptosis;C-Jun N-terminal kinase;cantharidic acid
    日期: 2018-04
    上傳時間: 2018-03-27T09:13:00Z (UTC)
    出版者: John Wiley and Sons Inc.
    ISSN: 15204081
    摘要: Cantharidin, a natural toxin from blister beetles, has shown potent anticancer activities on many solid tumor cells. Recently, cantharidin and its analogue, norcantharidin, were also shown to suppress nonsolid tumors such as chronic myeloid leukemia, acute myeloid leukemia (AML), and leukemic stem cells. However, there is no available information to address the effects of cantharidic acid (CAC), a hydrolysis product of cantharidin, on human AML cells. The present study showed that CAC, at a range of concentrations (0-20 μM), concentration-dependently inhibited cell proliferation in the HL-60 AML cell line. Western blot and flow cytometric assays demonstrated that CAC induced several features of apoptosis such as sub G1-phase cell increase, phosphatidylserine (PS) externalization, and significantly activated proapoptotic signaling including caspase-8, −9, and −3 activation and poly(ADP-ribose) polymerase (PARP) cleavage in HL-60 AML cells. Moreover, treatment of HL-60 cells with CAC induced concentration- and time- dependent activation of p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK). Only JNK-, but not p38 MAPK-specific inhibitor can reverse the CAC-induced activation of the caspase-8, −9, and −3. We concluded that CAC can induce apoptosis in human leukemic HL-60 cells via a caspases-dependent pathway, and that the apoptosis-inducing effect of CAC can be regulated by JNK activation signaling. © 2018 Wiley Periodicals, Inc.
    URI: https://www.doi.org/10.1002/tox.22537
    https://ir.csmu.edu.tw:8080/ir/handle/310902500/19055
    關聯: Environmental Toxicology Volume 33, Issue 4, April 2018, Pages 514-522
    顯示於類別:[附設醫院] 期刊論文

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