Chia Nan University of Pharmacy & Science Institutional Repository:Item 310902800/32545
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    標題: Piperlongumine induces autophagy in biliary cancer cells via reactive oxygen species-activated Erk signaling pathway
    作者: Chen, San-Yuan
    Huang, Hsin-Yi
    Lin, Han-Pei
    Fang, Chiung-Yao
    貢獻者: Chiayi Christian Hosp, Ditmanson Med Fdn, Dept Chinese Med
    Chia Nan Univ Pharm & Sci, Dept Sports Management
    Chiayi Christian Hosp, Ditmanson Med Fdn, Dept Med Res
    關鍵字: cholangiocarcinoma
    piperlongumine
    reactive oxygen species
    autophagy
    Erk signaling
    日期: 2019-11
    上傳時間: 2020-07-29 13:49:18 (UTC+8)
    出版者: SPANDIDOS PUBL LTD
    摘要: Biliary cancer (BC) is an aggressive neoplasm with high mortality. BC can be categorized into three groups: Intrahepatic cholangiocarcinoma (CCA; also known as bile duct cancer), extrahepatic cholangiocarcinoma and gallbladder cancer. Due to its heterogeneity and aggressiveness, the response to current chemotherapy and radiotherapy methods in patients with BC is poor. Therefore, there is an urgent requirement to develop drugs to treat BC. Piperlongumine (PL), a naturally occurring small molecule isolated from Piper longum L., exhibits anticancer activity by inducing reactive oxygen species (ROS) production. In the present study, the effects of PL on cell proliferation, cell cycle, apoptosis and autophagy in BC cells were investigated. PL induced BC cell death in a concentration- and time-dependent manner by inducing ROS production. PL induced cell cycle arrest in CCA cells (HuCCT-1) and gallbladder cancer cells (OCUG-1) cells, but with distinct cell cycle distribution profiles. PL caused G2/M cell cycle arrest in HuCCT-1 cells, and G0/G1 cell cycle arrest in OCUG-1 cells. PL induced apoptosis and autophagy; PL treatment induced accumulation of LC3-II in a concentration- and time-dependent manner. The Erk signaling pathway appeared to be involved in autophagy induction. Application of the ROS scavenger, N-acetyl-l-cysteine, to BC cells attenuated the cell death, cell cycle arrest, apoptosis and autophagy induced by PL treatment. These findings indicated that PL may be a potential agent for BC treatment in the future.
    關聯: International Journal of Molecular Medicine, v.44, n.5, pp.1687-1696
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