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.
基金:
National Basic Research Program of China (973 Program) [2010CB833804]; National Ocean 863 Project Ministry of Science and Technology of China [2011AA09070110, 2012AA092104]
第一作者机构:[2]Second Mil Med Univ, Dept Biochem & Mol Biol, Shanghai 200433, Peoples R China
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推荐引用方式(GB/T 7714):
Zhao Ying,Chen Huan,Shang Zhuo,et al.SD118-Xanthocillin X (1), a Novel Marine Agent Extracted from Penicillium commune, Induces Autophagy through the Inhibition of the MEK/ERK Pathway[J].MARINE DRUGS.2012,10(6):1345-1359.doi:10.3390/md10061345.
APA:
Zhao, Ying,Chen, Huan,Shang, Zhuo,Jiao, Binghua,Yuan, Bin...&Huang, Caiguo.(2012).SD118-Xanthocillin X (1), a Novel Marine Agent Extracted from Penicillium commune, Induces Autophagy through the Inhibition of the MEK/ERK Pathway.MARINE DRUGS,10,(6)
MLA:
Zhao, Ying,et al."SD118-Xanthocillin X (1), a Novel Marine Agent Extracted from Penicillium commune, Induces Autophagy through the Inhibition of the MEK/ERK Pathway".MARINE DRUGS 10..6(2012):1345-1359