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.
Francisco Estévez-Sarmiento  1 ,  Mercedes Said  1 ,  Ignacio Brouard  2 ,  Francisco León  2 ,  Celina García  3 ,  José Quintana  1 ,  Francisco Estévez  4
Affiliations
  • 1. Departamento de Bioquímica y Biología Molecular, Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Universidad de las Palmas de Gran Canaria, Paseo Blas Cabrera Felipe s/n, 35016 Las Palmas de Gran Canaria, Spain.
  • 2. Instituto de Productos Naturales y Agrobiología, CSIC, Avenida Astrofísico Francisco Sánchez 3, 38206 La Laguna, Tenerife, Spain.
  • 3. Instituto Universitario de Bio-Orgánica "Antonio González" (IUBO-AG), Departamento de Química Orgánica, Universidad de La Laguna, Avda. Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
  • 4. Departamento de Bioquímica y Biología Molecular, Unidad Asociada al Consejo Superior de Investigaciones Científicas (CSIC), Instituto Universitario de Investigaciones Biomédicas y Sanitarias, Universidad de las Palmas de Gran Canaria, Paseo Blas Cabrera Felipe s/n, 35016 Las Palmas de Gran Canaria, Spain. Electronic address: [email protected].
PMID: 29032930 DOI: 10.1016/j.bmc.2017.09.043
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.