Glycycoumarin exerts anti-liver cancer activity by directly targeting T-LAK cell-originated protein kinase

Abstract

// Xinhua Song 1 , Shutao Yin 1 , Enxiang Zhang 1 , Lihong Fan 2 , Min Ye 3 , Yong Zhang 4 , Hongbo Hu 1 1 Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China 2 College of Veterinary Medicine, China Agricultural University, Beijing 100193, China 3 The State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China 4 The Key Laboratory of RNA Biology, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China Correspondence to: Hongbo Hu, email: hongbo@cau.edu.cn Min Ye, email: yemin@bjmu.edu.cn Keywords: licorice, glycycoumarin, anti-liver cancer, T-LAK cell-originated protein kinase, p53 Received: June 03, 2016     Accepted: August 15, 2016     Published: August 25, 2016 ABSTRACT Glycycoumarin (GCM) is a major bioactive coumarin compound isolated from licorice and the anti-cancer activity of GCM has not been scientifically addressed. In the present study, we have tested the anti-liver cancer activity of GCM using both in vitro and in vivo models and found for the first time that GCM possesses a potent activity against liver cancer evidenced by cell growth inhibition and apoptosis induction in vitro and tumor reduction in vivo. Mechanistically, GCM was able to bind to and inactivate oncogenic kinase T-LAK cell-originated protein kinase (TOPK), which in turn led to activation of p53 pathway. Our findings supported GCM as a novel active compound that contributed to the anti-cancer activity of licorice and TOPK could be an effective target for hepatocellular carcinoma (HCC) treatment.