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Mar. Drugs 2012, 10(6), 1345-1359; doi:10.3390/md10061345
Article

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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2,* , 1,*  and 1,*
1 Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China 2 Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China 3 PET (Positron Emission Computed Tomography) Center, General Hospital of Chengdu Military Command, Chengdu, Sichuan 610083, China These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 24 April 2012 / Revised: 29 May 2012 / Accepted: 30 May 2012 / Published: 11 June 2012
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Abstract

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.
Keywords: SD118-xanthocillin X (1); autophagy; apoptosis; ERK; Beclin 1 SD118-xanthocillin X (1); autophagy; apoptosis; ERK; Beclin 1
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Zhao, Y.; Chen, H.; Shang, Z.; Jiao, B.; Yuan, B.; Sun, W.; Wang, B.; Miao, M.; Huang, C. SD118-Xanthocillin X (1), a Novel Marine Agent Extracted from Penicillium commune, Induces Autophagy through the Inhibition of the MEK/ERK Pathway. Mar. Drugs 2012, 10, 1345-1359.

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