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SD118-Xanthocillin X (1), a Novel Marine Agent Extracted from Penicillium commune, Induces Autophagy through the Inhibition of the MEK/ERK Pathway

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机构: [1]Chinese Acad Sci, Inst Oceanol, Key Lab Expt Marine Biol, Qingdao 266071, Peoples R China [2]Second Mil Med Univ, Dept Biochem & Mol Biol, Shanghai 200433, Peoples R China [3]Gen Hosp Chengdu Mil Command, PET Positron Emiss Computed Tomog Ctr, Chengdu 610083, Sichuan, Peoples R China
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关键词: SD118-xanthocillin X (1) autophagy apoptosis ERK Beclin 1

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A compound named SD118-xanthocillin X (1) (C18H12N2O2), isolated from Penicillium commune in a deep-sea sediment sample, has been shown to inhibit the growth of several cancer cell lines in vitro. In the present study, we employed a growth inhibition assay and apoptotic analysis to identify the biological effect and detailed mechanism of SD118-xanthocillin X (1) in human hepatocellular carcinoma (HepG2) cells. SD118-xanthocillin X (1) demonstrated a concentration-dependent inhibitory effect on the growth of HepG2 cells and caused slight cellular apoptosis and significantly induced autophagy. Autophagy was detected as early as 12 h by the conversion of microtubule-associated protein 1 light chain 3 (LC3-I) to LC3-II, following cleavage and lipid addition to LC3-I. The pharmacological autophagy inhibitor 3-methyladenine largely attenuates the growth inhibition and autophagic effect of SD118-xanthocillin X (1) in HepG2 cells. Our data also indicated that the autophagic effect of SD118-xanthocillin X (1) occurs via the down-regulation of the MEK/ERK signaling pathway and the up-regulated class III PI3K/Beclin 1 signaling pathway.

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出版当年[2012]版:
大类 | 3 区 医学
小类 | 2 区 药物化学
最新[2023]版:
大类 | 2 区 医学
小类 | 2 区 药物化学 2 区 药学
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出版当年[2012]版:
Q1 CHEMISTRY, MEDICINAL
最新[2023]版:
Q1 CHEMISTRY, MEDICINAL Q1 PHARMACOLOGY & PHARMACY

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第一作者机构: [2]Second Mil Med Univ, Dept Biochem & Mol Biol, Shanghai 200433, Peoples R China
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