Deacetylisovaltratum disrupts microtubule dynamics and causes G2/M-phase arrest in human gastric cancer cells in vitro

Acta Pharmacol Sin. 2016 Dec;37(12):1597-1605. doi: 10.1038/aps.2016.91. Epub 2016 Sep 26.

Abstract

Aim: Deacetylisovaltratum (DI) is isolated from the traditional Chinese herbal medicine Patrinia heterophylla Bunge, which exhibits anti-cancer activity. Here, we investigated the effects of DI on human gastric carcinoma cell lines in vitro and elucidated its anti-cancer mechanisms.

Methods: Human gastric carcinoma AGS and HGC-27 cell lines were treated with DI, and cell viability was detected with MTT assay. Cell cycle stages, apoptosis and mitochondrial membrane potential were measured using flow cytometry. Protein levels were analyzed by Western blotting. Tubulin polymerization assays and immunofluorescence were used to characterize the tubulin polymerization process.

Results: DI inhibited the cell viability of AGS and HGC-27 cells in a dose- and time-dependent manner with IC50 values of 12.0 and 28.8 μmol/L, respectively, at 24 h of treatment. Treatment with DI (10-100 μmol/L) dose-dependently promoted tubulin polymerization, and induced significant G2/M cell cycle arrest in AGS and HGC-27 cells. Moreover, DI treatment disrupted mitochondrial membrane potential and induced caspase-dependent apoptosis in AGS and HGC-27 cells.

Conclusion: DI induces G2/M-phase arrest by disrupting tubulin polymerization in human gastric cancer cells, which highlights its potent anti-cancer activity and potential application in gastric cancer therapy.

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Line, Tumor / drug effects
  • Cell Survival / drug effects
  • G2 Phase Cell Cycle Checkpoints / drug effects*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Potentials / drug effects
  • Stomach Neoplasms / drug therapy*
  • Tubulin / chemistry
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology*

Substances

  • Antineoplastic Agents
  • Tubulin
  • Tubulin Modulators