Jujube leaf green tea extracts inhibits hepatocellular carcinoma cells by activating AMPK

// HX Liu 1 , MQ Xu 1 , SP Li 1 , S Tian 1 , MX Guo 1 , JY Qi 1 , CJ He 1 and XS Zhao 1 1 Jujube Scientific Research and Applied Center, Life Science College, Luoyang Normal University, Luoyang, China Correspondence to: Zhao XS, email: zhaoxs2017@163.com ; hongxialiu2015@163.com Keywords: jujube leaf green tea extracts; hepatocellular carcinoma; AMPK signaling Received: November 01, 2017      Accepted: November 13, 2017      Published: November 30, 2017 ABSTRACT Here we evaluated the anti-hepatocellular carcinoma activity by the Jujube leaf green tea extracts (JLGTE). We showed that JLGTE exerted anti-proliferative, cytotoxic and pro-apoptotic activities against HepG2 and primary human hepatocellular carcinoma cells. It was however non-cytotoxic to the normal hepatocytes. JLGTE activated AMP-activated protein kinase (AMPK) signaling, which was required for its cytotoxicity against hepatocellular carcinoma cells. Silence of AMPKα1, via targeted short hairpin RNAs or CRISPR-Cas9 genome editing, inhibited JLGTE-induced AMPK activation and HepG2 cell apoptosis. Further, in-activation of AMPK by a dominant negative AMPKα1 (T172A) also alleviated JLGTE’s cytotoxicity against HepG2 cells. On the other hand, forced-activation of AMPK by introduction of a constitutively-active AMPKα1 (T172D) mimicked JLGTE’s actions and led to HepG2 cell apoptosis. These results suggest that JLGTE inhibits human hepatocellular carcinoma cells possibly via activating AMPK.