3′-Hydroxy-3, 4′-dimethoxyflavone blocks tubulin polymerization and is a potent apoptotic inducer in human SK-MEL-1 melanoma cells. Issue 21 (1st November 2017)

• Record Type: Journal Article
• Authors: Estévez-Sarmiento, Francisco; Said, Mercedes; Brouard, Ignacio; León, Francisco; García, Celina; Quintana, José; Estévez, Francisco
• Is Part Of: Bioorganic & medicinal chemistry. Volume 25:Issue 21(2017)
• Page Start: 6060
• Page End: 6070
• Publication Date: 2017-11-01
• Subjects: MTT 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide -- PI propidium iodide; Apoptosis -- Caspases -- Cytotoxicity -- Flavonoids -- Melanoma; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2017.09.043
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Highlights: 3′-Hydroxy-3, 4′-dimethoxyflavone is an apoptotic inducer of melanoma cells. It causes arrest in the G2 -M phase of the cell cycle. Cell death was associated with the activation of both initiator caspases. It activates the extrinsic and the intrinsic apoptotic pathways of cell death. 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 (flavonoid7a ) 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 flavonoid7a 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.