SD118-xanthocillin X (1), a novel marine agent extracted from Penicillium commune, induces autophagy through the inhibition of the MEK/ERK pathway.

Abstract

A compound named SD118-xanthocillin X (1) (C(18)H(12)N(2)O(2)), 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.

• Authors: Ying Zhao, Huan Chen, Zhuo Shang, Binghua Jiao, Bin Yuan, Weizhang Sun, Bingui Wang, Mingyong Miao, Caiguo Huang
• Journal: Marine drugs (Mar Drugs) Vol. 10 Issue 6 Pg. 1345-1359 (Jun 2012) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 22822377 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• BECN1 protein, human
• Beclin-1
• Biological Products
• Butadienes
• Membrane Proteins
• Phenols
• xantocillin
• 3-methyladenine
• Phosphatidylinositol 3-Kinases
• Adenine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Apoptosis (drug effects)
• Apoptosis Regulatory Proteins (metabolism)
• Aquatic Organisms (chemistry)
• Autophagy (drug effects)
• Beclin-1
• Biological Products (chemistry, isolation & purification, pharmacology)
• Butadienes (chemistry, isolation & purification, pharmacology)
• Cell Line, Tumor
• Down-Regulation (drug effects)
• Hep G2 Cells
• Humans
• MAP Kinase Signaling System (drug effects)
• Membrane Proteins (metabolism)
• Penicillium (chemistry)
• Phenols (chemistry, isolation & purification, pharmacology)
• Phosphatidylinositol 3-Kinases (metabolism)
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)