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

Marine Drugs

Ying Zhao¹  Huan Chen¹  Zhuo Shang²  Binghua Jiao¹  Bin Yuan¹  Weizhang Sun³  Bingui Wang²  Mingyong Miao¹ 

[1] 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;

关键词: SD118-xanthocillin X (1);    autophagy;    apoptosis;    ERK;    Beclin 1;   

DOI  :  10.3390/md10061345

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.