In vitro inhibitory effects of terpenoids from Chloranthus multistachys on epithelial-mesenchymal transition via down-regulation of Runx2 activation in human breast cancer

Phytomedicine. 2015 Jan 15;22(1):165-72. doi: 10.1016/j.phymed.2014.11.010. Epub 2014 Nov 27.

Abstract

From Chloranthus multistachys, three terpenoids - lupeol (1), henrilabdane B (2), and istanbulin A (3) were isolated. Structures of compounds were established by NMR and MS. We reported here that ISTA (3) suppressed cell invasion, but lupeol (1) and henrilabdane B (2) did not. Furthermore, ISTA significantly inhibited the ability of adhesion and migration in vitro. Next, mechanisms of ISTA-induced inhibitory effects on in vitro metastasis were investigated. Sequential treatment data revealed that ISTA dramatically inhibited EGF-induced EMT. Western blot indicated that ISTA also significantly suppressed expression of E-cadherin, vimentin, and slug. In addition, ISTA inhibited Runx2 activation and phosph-Runx2 expression. Collectively, ISTA exhibited significant inhibitory effects on in vitro metastatic potential via inducing EMT inhibition, which may be associated with inhibition of transcriptional activity of Runx2.

Keywords: Chloranthus multistachys; EMT; In vitro; Istanbulin A; Runx2; Terpenoids.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Breast Neoplasms / metabolism*
  • Cell Line, Tumor
  • Core Binding Factor Alpha 1 Subunit / genetics
  • Core Binding Factor Alpha 1 Subunit / metabolism*
  • Diterpenes / pharmacology
  • Down-Regulation
  • Epithelial-Mesenchymal Transition / drug effects*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Magnoliopsida / chemistry*
  • Molecular Structure
  • Pentacyclic Triterpenes / pharmacology
  • Plant Components, Aerial / chemistry
  • Sesquiterpenes / pharmacology
  • Terpenes / pharmacology*

Substances

  • Antineoplastic Agents, Phytogenic
  • Core Binding Factor Alpha 1 Subunit
  • Diterpenes
  • Pentacyclic Triterpenes
  • RUNX2 protein, human
  • Sesquiterpenes
  • Terpenes
  • istanbulin A
  • lupeol