Actinidia chinensis Planch root extract attenuates proliferation and metastasis of hepatocellular carcinoma by inhibiting epithelial-mesenchymal transition

J Ethnopharmacol. 2019 Mar 1:231:474-485. doi: 10.1016/j.jep.2018.11.014. Epub 2018 Nov 8.

Abstract

Ethno-pharmacological relevance: Numerous studies have demonstrated the potent anticancer activity of various Chinese herbs. Actinidia chinensis Planch root (acRoots), a traditional Chinese medicine, functions as an antitumor and detoxifying agent and plays a role in diuresis and hemostasis. Treatment with acRoots confers strong inhibition of tumor growth in various forms of cancer. Here, we evaluated the anticancer activity and molecular mechanisms of Actinidia chinensis Planch root extract (acRoots) on hepatocellular carcinoma (HCC).

Materials and methods: Our previous study used mRNA chip analyses to identify the genes regulated by acRoots. Further analyses of the altered genes identified a key regulator of genes in response to acRoots. Here, the effects of acRoots on HCC cell proliferation, migration, invasion, and apoptosis were evaluated by cell counting, Transwell and apoptosis assays. In addition, the in vivo anti-HCC effects of acRoots were investigated using an HCC animal model. The expression of a key regulator of genes in response to acRoots was analyzed using quantitative polymerase chain reaction and western blotting.

Results: Treatment with acRoots (10 mg/mL) had no cytotoxicity in L02 cells and had a positive effect on L02 cell viability; however, it significantly inhibited HCC cell proliferation. Treatment with acRoots downregulated DLX2 gene expression in HCC cells, and high DLX2 expression was associated with advanced stage and poor prognosis in patients with HCC. Treatment with acRoots inhibited proliferation, invasion and migration, clonality, and the epithelial-to-mesenchymal transition, and promoted the apoptosis of HCC cells by downregulating DLX2 expression. HCC cells with higher DLX2 expression were more sensitive to acRoots.

Conclusions: acRoots inhibited the malignant biological behavior of HCC cells via regulation of the epithelial-mesenchymal transition (EMT) by DLX2.

Keywords: Actinidia chinensis Planch root; DLX2; EMT; Hepatocellular carcinoma; Invasion; Metastasis; Natural anti-cancer drugs.

MeSH terms

  • Actinidia*
  • Animals
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Carcinoma, Hepatocellular* / drug therapy
  • Carcinoma, Hepatocellular* / genetics
  • Carcinoma, Hepatocellular* / pathology
  • Cell Line
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Epithelial-Mesenchymal Transition / drug effects
  • Gene Expression Regulation, Neoplastic / drug effects
  • Homeodomain Proteins / genetics
  • Humans
  • Liver Neoplasms* / drug therapy
  • Liver Neoplasms* / genetics
  • Liver Neoplasms* / pathology
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Plant Extracts* / pharmacology
  • Plant Extracts* / therapeutic use
  • Plant Roots
  • Transcription Factors / genetics

Substances

  • Antineoplastic Agents
  • DLX2 protein, human
  • Homeodomain Proteins
  • Plant Extracts
  • Transcription Factors