4'-methoxy-2-styrylchromone a novel microtubule-stabilizing antimitotic agent

Biochem Pharmacol. 2008 Feb 15;75(4):826-35. doi: 10.1016/j.bcp.2007.10.014. Epub 2007 Oct 22.

Abstract

4'-methoxy-2-styrylchromone, a new synthetic chromone was identified as a selective proliferation inhibitor of human tumor (MCF-7 and NCI-H460) cell lines than to non-tumor cells (MRC-5). The antiproliferative activity of this chromone was also extensive to peripheral human lymphocytes. 4'-Methoxy-2-styrylchromone was found to block tumor cells in the G2/M phase of the cell cycle. The G2/M arrest of NCI-H460 cells was dose- and time-dependent, reaching a maximum after 12-h treatment while MCF-7 cells reached the maximum value of G2/M accumulation only after a 24-h treatment. Chromone-treated cells evidenced a high frequency of cells in prometaphase, indicating progression beyond G2 and arrest early in mitosis. This mitotic arrest was associated with abnormal mitotic spindles characterized by the formation of a monopolar structure, suggesting that the chromone interferes with microtubules. The results of an in vitro tubulin polymerization assay showed that this chromone stabilizes microtubules in a manner similar to paclitaxel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Chromones / chemistry
  • Chromones / pharmacology*
  • Humans
  • Lymphocytes / cytology
  • Lymphocytes / drug effects*
  • Microscopy, Fluorescence
  • Microtubules / drug effects*
  • Mitotic Index
  • Molecular Structure
  • Styrenes / chemistry
  • Styrenes / pharmacology*
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology*

Substances

  • 4'-methoxy-2-styrylchromone
  • Chromones
  • Styrenes
  • Tubulin Modulators