Volatile oil from Saussurea lappa exerts antitumor efficacy by inhibiting epithelial growth factor receptor tyrosine kinase-mediated signaling pathway in hepatocellular carcinoma

// Xuejing Lin 1, * , Zhangxiao Peng 1, * , Xiaohui Fu 2, * , Chunying Liu 1 , Yang Xu 1 , Weidan Ji 1 , Jianhui Fan 1 , Lei Chen 1 , Lin Fang 3 , Yao Huang 2 , Changqing Su 1, 3 1 Department of Molecular Oncology, Eastern Hepatobiliary Surgical Hospital & National Center of Liver Cancer, Second Military Medical University, Shanghai 200438, China 2 Department of Biliary Tract Surgery, Eastern Hepatobiliary Surgical Hospital, Second Military Medical University, Shanghai 200438, China 3 Jiangsu Center for The Collaboration and Innovation of Cancer Biotherapy, Xuzhou Medical College, Xuzhou 221002, China * These authors have contributed equally to this work Correspondence to: Changqing Su, email: suchangqing@gmail.com Yao Huang, email: huangyaodr@msn.com Keywords: VOSL, hepatocellular carcinoma, epithelial growth factor receptor, signaling, xenograft model Received: June 20, 2016     Accepted: October 19, 2016     Published: October 28, 2016 ABSTRACT Hepatocellular carcinoma (HCC) treatment remains lack of effective chemotherapeutic drugs, therefore, discovering novel anti-HCC drugs is a very attractive and urgent task. In this study, we reported VOSL (volatile oil from Saussurea lappa root) exhibits potent therapeutic effect on SMMC-7721 xenografts without obvious side effects. In the in vitro experiments, VOSL inhibited HCC cell proliferation by arresting cell cycle at S and G2/M phases, and induced HCC cell apoptosis by activating the Caspase3 pathway. VOSL also decreased the capability of HCC cell migration and invasion through MMP-9 depression. Moreover, mechanistic study indicated that VOSL can act as an epithelial growth factor receptor (EGFR) inhibitor to suppress EGFR activation and then to suppress its downstream MEK/P38 and PI3-K/Akt pathways. These results suggested that VOSL may be a novel anti-HCC drug candidate.