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

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

Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China
Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
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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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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MDPI and ACS Style

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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