title: 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: Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Ying
authors: Y
authors: Zhao
authors: Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Huan
authors: H
authors: Chen
authors: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
authors: Zhuo
authors: Z
authors: Shang
authors: Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Binghua
authors: B
authors: Jiao
authors: Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Bin
authors: B
authors: Yuan
authors: PET (Positron Emission Computed Tomography) Center, General Hospital of Chengdu Military Command, Chengdu, Sichuan 610083, China.
authors: Weizhang
authors: W
authors: Sun
authors: Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China.
authors: Bingui
authors: B
authors: Wang
authors: Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Mingyong
authors: M
authors: Miao
authors: Department of Biochemistry and Molecular Biology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors: Caiguo
authors: C
authors: Huang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D059001:Aquatic Organisms / Q000737:chemistry; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002070:Butadienes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects; D056945:Hep G2 Cells; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008565:Membrane Proteins / Q000378:metabolism; D010407:Penicillium / Q000737:chemistry*; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D001688:Biological Products; D002070:Butadienes; D008565:Membrane Proteins; D010636:Phenols; C493153:xantocillin; C025946:3-methyladenine; D019869:Phosphatidylinositol 3-Kinases; D000225:Adenine