3'-Hydroxy-3,4'-dimethoxyflavone blocks tubulin polymerization and is a potent apoptotic inducer in human SK-MEL-1 melanoma cells

Bioorg Med Chem. 2017 Nov 1;25(21):6060-6070. doi: 10.1016/j.bmc.2017.09.043. Epub 2017 Oct 3.

Abstract

Flavonoids are naturally occurring polyphenolic compounds and are among the most promising anticancer agents. A series of flavonols and their 3-methyl ether derivatives were synthesized and assessed for cytotoxicity. It was found that 3'-hydroxy-3,4'-dimethoxyflavone (flavonoid 7a) displayed strong cytotoxicity against human SK-MEL-1 melanoma cells and blocked tubulin polymerization, but had no significant cytotoxic effects against quiescent or proliferating human peripheral blood mononuclear cells. Our analyses showed that flavonoid 7a induces G2-M cell cycle arrest and apoptosis in melanoma cells which is associated with cytochrome c release and activation of both extrinsic and intrinsic apoptotic pathways of cell death.

Keywords: Apoptosis; Caspases; Cytotoxicity; Flavonoids; Melanoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Flavones / chemical synthesis
  • Flavones / chemistry
  • Flavones / pharmacology*
  • Humans
  • Melanoma / drug therapy*
  • Melanoma / pathology
  • Microscopy, Fluorescence
  • Molecular Structure
  • Polymerization / drug effects
  • Structure-Activity Relationship
  • Tubulin / metabolism*
  • Tumor Cells, Cultured

Substances

  • 3'-hydroxy-3,4'-dimethylflavone
  • Flavones
  • Tubulin