title: Sauchinone exerts anticancer effects by targeting AMPK signaling in hepatocellular carcinoma cells.
abstract: Sauchinone is a pharmacologically active compound isolated from Saururus chinensis, which has been used as a traditional Oriental medicine to treat fever, jaundice, and various inflammatory diseases. In this study, we investigated the effect of sauchinone against hepatocellular carcinoma (HCC) and sought to elucidate the mechanism involved. Cell viability was measured by an MTT assay. Cell cycle distributions and the mitochondrial membrane potential were analyzed using flow cytometry. Cell death was analyzed by annexin V assay, 4',6-diamidino-2-phenylindole staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Protein and mRNA levels were assessed by western blot and real-time PCR, respectively. Malignant properties were investigated by a wound healing migration assay and invasion assay. Sauchinone suppressed the proliferation of human HCC cells in a dose-dependent manner. Moreover, it induced the G0/G1 phase cell cycle arrest and mitochondrial dysfunction and then triggered the apoptosis by activating the JNK/p38 pathway in Huh-7 cells. In addition, sauchinone induced the activation of the AMP-activated protein kinase (AMPK) pathway, and compound C (an AMPK inhibitor) blocked the sauchinone-induced mitochondrial dysfunction. The AMPK activation by sauchinone inhibited the phosphorylation of the mammalian target of rapamycin (mTOR) and its downstream targets, such as ribosomal protein S6 kinase 1 and eIF4E-binding protein 1. Furthermore, sauchinone attenuated key proangiogenic factors, including hypoxia-inducible factor-1α, vascular endothelial growth factor, and plasminogen activator inhibitor-1, resulting in decreased migration and invasion of HCC cells. These results provide evidence for sauchinone to be considered as a potent anticancer agent by targeting of the AMPK-mTOR pathway in HCC.
authors.affiliation: College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
authors.forename: Young Woo
authors.initials: YW
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea.
authors.forename: Eun Jeong
authors.initials: EJ
authors.lastname: Jang
authors.affiliation: Department of Medicine, College of Medicine, Dongguk University, Goyang 10326, Republic of Korea.
authors.forename: Chang-Hyun
authors.initials: CH
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Dongguk University, Goyang 10326, Republic of Korea. Electronic address: jh1548@dongguk.ac.kr.
authors.forename: Ju-Hee
authors.initials: JH
authors.lastname: Lee
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004149:Dioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D015398:Signal Transduction / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D004149:Dioxoles; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A; C410958:sauchinone; D055372:AMP-Activated Protein Kinases
keywords: AMPK; Anti-cancer; Apoptosis; Hepatocellular carcinoma; Sauchinone