PMID- 27871897 OWN - NLM STAT- MEDLINE DCOM- 20170207 LR - 20171116 IS - 1872-7786 (Electronic) IS - 0009-2797 (Linking) VI - 261 DP - 2017 Jan 5 TI - Sauchinone exerts anticancer effects by targeting AMPK signaling in hepatocellular carcinoma cells. PG - 108-117 LID - S0009-2797(16)30594-4 [pii] LID - 10.1016/j.cbi.2016.11.016 [doi] AB - 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-1alpha, 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. CI - Copyright (c) 2016 Elsevier Ireland Ltd. All rights reserved. FAU - Kim, Young Woo AU - Kim YW AD - College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea. FAU - Jang, Eun Jeong AU - Jang EJ AD - College of Korean Medicine, Daegu Haany University, Gyeongsan 38610, Republic of Korea. FAU - Kim, Chang-Hyun AU - Kim CH AD - Department of Medicine, College of Medicine, Dongguk University, Goyang 10326, Republic of Korea. FAU - Lee, Ju-Hee AU - Lee JH AD - College of Korean Medicine, Dongguk University, Goyang 10326, Republic of Korea. Electronic address: jh1548@dongguk.ac.kr. LA - eng PT - Journal Article DEP - 20161118 PL - Ireland TA - Chem Biol Interact JT - Chemico-biological interactions JID - 0227276 RN - 0 (Antineoplastic Agents) RN - 0 (Benzopyrans) RN - 0 (Dioxoles) RN - 0 (HIF1A protein, human) RN - 0 (Hypoxia-Inducible Factor 1, alpha Subunit) RN - 0 (Vascular Endothelial Growth Factor A) RN - 0 (sauchinone) RN - EC 2.7.11.31 (AMP-Activated Protein Kinases) SB - IM MH - AMP-Activated Protein Kinases/*metabolism MH - Antineoplastic Agents/pharmacology/*therapeutic use MH - Apoptosis/drug effects MH - Benzopyrans/pharmacology/*therapeutic use MH - Carcinoma, Hepatocellular/*drug therapy/*enzymology/pathology MH - Cell Cycle/drug effects MH - Cell Line, Tumor MH - Cell Movement/drug effects MH - Cell Proliferation/drug effects MH - Dioxoles/pharmacology/*therapeutic use MH - Enzyme Activation/drug effects MH - Humans MH - Hypoxia-Inducible Factor 1, alpha Subunit/metabolism MH - Liver Neoplasms/*drug therapy/*enzymology/pathology MH - Neoplasm Invasiveness MH - Signal Transduction/*drug effects MH - Vascular Endothelial Growth Factor A/metabolism OTO - NOTNLM OT - AMPK OT - Anti-cancer OT - Apoptosis OT - Hepatocellular carcinoma OT - Sauchinone EDAT- 2016/11/23 06:00 MHDA- 2017/02/09 06:00 CRDT- 2016/11/23 06:00 PHST- 2016/06/13 00:00 [received] PHST- 2016/11/08 00:00 [revised] PHST- 2016/11/16 00:00 [accepted] PHST- 2016/11/23 06:00 [pubmed] PHST- 2017/02/09 06:00 [medline] PHST- 2016/11/23 06:00 [entrez] AID - S0009-2797(16)30594-4 [pii] AID - 10.1016/j.cbi.2016.11.016 [doi] PST - ppublish SO - Chem Biol Interact. 2017 Jan 5;261:108-117. doi: 10.1016/j.cbi.2016.11.016. Epub 2016 Nov 18.