Oleocanthal inhibits growth and metastasis by blocking activation of STAT3 in human hepatocellular carcinoma

// Tiemin Pei 1, * , Qinghui Meng 1, * , Jihua Han 1, * , Haobo Sun 1 , Long Li 1 , Ruipeng Song 1 , Boshi Sun 1 , Shangha Pan 1 , Desen Liang 1 , Lianxin Liu 1 1 Key Laboratory of Hepatosplenic Surgery, Ministry of Education, Department of General Surgery, the First Affiliated Hospital of Harbin Medical University, Harbin, China * These authors contributed equally to this work Correspondence to: Lianxin Liu, email: liulx@ems.hrbmu.edu.cn Desen Liang, email: liangdesen2015@163.com Keywords: hepatocellular carcinoma, (-)-Oleocanthal, tumor growth, tumor metastasis, STAT3 Received: January 07, 2016      Accepted: May 12, 2016      Published: June 02, 2016 ABSTRACT We explored the anti-cancer capacity of (-)-oleocanthal in human hepatocellular carcinoma (HCC). (-)-Oleocanthal inhibited proliferation and cell cycle progression and induced apoptosis in HCC cells in vitro and suppressed tumor growth in an orthotopic HCC model. (-)-Oleocanthal also inhibited HCC cell migration and invasion in vitro and impeded HCC metastasis in an in vivo lung metastasis model. ( )-Oleocanthal acted by inhibiting epithelial-mesenchymal transition (EMT) through downregulation Twist, which is a direct target of STAT3. (-)-Oleocanthal also reduced STAT3 nuclear translocation and DNA binding activity, ultimately downregulating its downstream effectors, including the cell cycle protein Cyclin D1, the anti-apoptotic proteins Bcl-2 and survivin, and the invasion-related protein MMP 2. Overexpression of constitutively active STAT3 partly reversed the anti cancer effects of (-)-oleocanthal, which inhibited STAT3 activation by decreasing the activities of JAK1 and JAK2 and increasing the activity of SHP-1. These data suggest that (-)-oleocanthal may be a promising candidate for HCC treatment.