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

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.

• Authors: Francisco Estévez-Sarmiento, Mercedes Said, Ignacio Brouard, Francisco León, Celina García, José Quintana, Francisco Estévez
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 25 Issue 21 Pg. 6060-6070 (11 01 2017) ISSN: 1464-3391 [Electronic] England
• PMID: 29032930 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Ltd. All rights reserved.

Chemical References

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

Topics

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