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

Oncotarget. 2016 Nov 29;7(48):79761-79773. doi: 10.18632/oncotarget.12962.

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.

Keywords: VOSL; epithelial growth factor receptor; hepatocellular carcinoma; signaling; xenograft model.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / isolation & purification
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Antineoplastic Agents, Phytogenic / therapeutic use*
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • ErbB Receptors / metabolism
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Oils, Volatile / isolation & purification
  • Oils, Volatile / pharmacology
  • Oils, Volatile / therapeutic use*
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use
  • Saussurea / chemistry*
  • Signal Transduction / drug effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Oils, Volatile
  • Plant Extracts
  • ErbB Receptors