Evaluation of 2',4'-dihydroxy-3,4,5-trimethoxychalcone as antimitotic agent that induces mitotic catastrophe in MCF-7 breast cancer cells

Toxicol Lett. 2014 Sep 2;229(2):393-401. doi: 10.1016/j.toxlet.2014.06.016. Epub 2014 Jun 23.

Abstract

We previously reported the synthesis and the anti-proliferative action of 2',4'-dihydroxy-3,4,5-trimethoxychalcone. Here we reported its mechanism of action on MCF-7 cells. The compound induced aberrant spindles, and arrested cells at metaphase/anaphase boundary with accumulation of checkpoint proteins Mad2, Bub1 and BubR1. Live cell imaging revealed that the compound sustained a prolonged mitotic arrest, followed by massive cell death. The results indicate that 2',4'-dihydroxy-3,4,5-trimethoxychalcone exerts its anti-proliferative activity by affecting microtubules and causing mitotic catastrophe, and thus has the potential for antitumor activity.

Keywords: 2′,4′-Dihydroxy-3,4,5-trimethoxychalcone; Anti-microtubule; Apoptosis; Cancer chemotherapy; Mitotic arrest; Mitotic catastrophe.

Publication types

  • Research Support, Non-U.S. Gov't
  • Video-Audio Media

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Antimitotic Agents / pharmacology
  • Antimitotic Agents / toxicity*
  • Breast Neoplasms / drug therapy*
  • Cell Death / drug effects
  • Chalcones / pharmacology
  • Chalcones / toxicity*
  • Female
  • Fluorescent Antibody Technique
  • Humans
  • In Situ Nick-End Labeling
  • MCF-7 Cells
  • Microscopy, Video
  • Mitosis / drug effects*
  • Spindle Apparatus / drug effects

Substances

  • 2',4'-dihydroxy-3,4,5-trimethoxychalcone
  • Antimitotic Agents
  • Chalcones