caa a22 4500 606233857 CHVBK 20210128101234.0 cr unu---uuuuu 210128e20150401xx s 000 0 eng 10.1007/s11010-014-2314-x doi (NATIONALLICENCE)springer-10.1007/s11010-014-2314-x Ursolic acid inhibited growth of hepatocellular carcinoma HepG2 cells through AMPKα-mediated reduction of DNA methyltransferase 1 [Elektronische Daten] [Yinyi Yie, Shunyu Zhao, Qin Tang, Fang Zheng, Jingjing Wu, LiJuan Yang, ShiGuan Deng, Swei Hann] Hepatocellular carcinoma (HCC), the major histological subtype of primary liver cancer, remains one of the most common malignancies worldwide. Due to the complicated pathogenesis of this malignancy, the outcome for comprehensive treatment is limited. Chineseherbalmedicine(CHM) is emerging as a promising choice for its multi-targets and coordinated intervention effects againstHCC. Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid found in CHM, exerts anti-tumor effects and is emerging as an effective compound for cancer prevention and therapy. However, the molecular mechanisms underlying the action of UA remain largely unknown. In this study, we showed that UA inhibited the growth of HCC cells and induced apoptosis in the dose- and time-dependent fashion. Furthermore, we found that UA induced phosphorylation of AMP-activated protein kinase alpha (AMPKα) and suppressed the protein expression of DNA methyltransferase 1 (DNMT1) in the dose-dependent manner. The inhibitor of AMPK, compound C blocked, while an activator of AMPK, metformin augmented the effect of UA on DNMT1 expression. In addition, UA suppressed the expression of transcription factor Sp1. Conversely, overexpression of Sp1 reversed the effect of UA on DNMT1 expression and cell growth. Collectively, our results show for the first time that UA inhibits growth of HCC through AMPKα-mediated inhibition of Sp1; this in turn results in inhibition of DNMT1. This study reveals a potential novel mechanism by which UA controls growth of HCC cells and suggests that DNMT1 could be novel target for HCCchemoprevention and treatment. Springer Science+Business Media New York, 2014 Human hepatocellular carcinoma cells nationallicence AMPKα nationallicence DNMT1 nationallicence Ursolic acid nationallicence Sp1 nationallicence Yie Yinyi Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut Zhao Shunyu Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut Tang Qin Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut Zheng Fang Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut Wu Jingjing Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut Yang LiJuan Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut Deng ShiGuan The Animal Research Center, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut Hann Swei Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 402/1-2(2015-04-01), 63-74 0300-8177 402:1-2<63 2015 402 11010 https://doi.org/10.1007/s11010-014-2314-x text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s11010-014-2314-x text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Yie Yinyi Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Zhao Shunyu Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Tang Qin Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Zheng Fang Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Wu Jingjing Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Yang LiJuan Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Deng ShiGuan The Animal Research Center, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut NATIONALLICENCE 700 1- Hann Swei Laboratory of Tumor Biology, Guangdong Provincial Hospital of Chinese Medicine, The Second Clinical Medical College, University of Guangzhou Traditional Chinese Medicine, 510120, Guangzhou, Guangdong, China aut NATIONALLICENCE 773 0- Molecular and Cellular Biochemistry Springer US; http://www.springer-ny.com 402/1-2(2015-04-01), 63-74 0300-8177 402:1-2<63 2015 402 11010