Lobetyol activate MAPK pathways associated with G1/S cell cycle arrest and apoptosis in MKN45 cells in vitro and in vivo

Biomed Pharmacother. 2016 Jul:81:120-127. doi: 10.1016/j.biopha.2016.03.046. Epub 2016 Apr 13.

Abstract

Aim: The agent lobetyol, which is isolated from Lobelia chinensis, was previously shown to be cytotoxicity againts several cancer cell lines in published report. Today, we perform a study in vitro and in vivo to analyze its anti-carcinoma effect in MKN45 cells and to explore the molecular mechanism.

Main methods: The growth inhibition of lobetyol on MKN45 cells was analyzed with MTT and flow cytometry. Hoechst 33342 staining and TUNEL cover glass staining were used to provide the visual evidence of apoptosis. Western blotting assay was performed to study the activation or blocking of related signaling pathways.

Key findings: Lobetyol induce apoptosis and cell cycle arrest in a time- and dose-dependent manner in MKN45 cells in our study. This process is mediated by the MAPK signaling pathways. This study confirmed the cytotoxicity of lobetyol in MKN45 cells and provided an insight into the molecular mechanism, which demonstrates the potential of lobetyol as an anti-tumor agent.

Keywords: Apoptosis; Cell cycle arrest; Lobetyol; MAPK; MKN45.

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Flow Cytometry
  • G1 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • MAP Kinase Signaling System / drug effects*
  • Mice, Nude
  • Polyynes / chemistry
  • Polyynes / pharmacology*
  • S Phase Cell Cycle Checkpoints / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Polyynes
  • Caspases