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

doi:10.3390/md10061345

This article is

freely available
re-usable

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

Ying Zhao^1,†, Huan Chen^1,†, Zhuo Shang², Binghua Jiao¹, Bin Yuan¹, Weizhang Sun³, Bingui Wang^2,* , Mingyong Miao^1,* and Caiguo Huang^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; in revised form: 29 May 2012 / Accepted: 30 May 2012 / Published: 11 June 2012

Download PDF Full-Text [1777 KB, uploaded 11 June 2012 13:42 CEST]

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

Article Statistics

Click here to load and display the download statistics.

Cite This Article

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.

AMA 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. Marine Drugs. 2012; 10(6):1345-1359.

Chicago/Turabian Style

Zhao, Ying; Chen, Huan; Shang, Zhuo; Jiao, Binghua; Yuan, Bin; Sun, Weizhang; Wang, Bingui; Miao, Mingyong; 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." Mar. Drugs 10, no. 6: 1345-1359.

Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert