Induction of G2/M phase arrest and apoptosis by the flavonoid tamarixetin on human leukemia cells.

Authors:
Fabio Nicolini
Fabio Nicolini
Centro de Investigaciones Biológicas
Olga Burmistrova
Olga Burmistrova
Departamento de Bioquímica y Biología Molecular
Fernando Torres
Fernando Torres
University of Texas Southwestern Medical Center
United States
Cristina Hernandez
Cristina Hernandez
Vall d'Hebron Research Institute
Barcelona | Spain
Jose Quintana
Jose Quintana
Hospital Galdakao-Usansolo (Osakidetza)-Red de Investigación en Servicios de Salud en Enfermedades Crónicas
Spain
Francisco Estevez
Francisco Estevez
Juan Canalejo Hospital
Spain

Mol Carcinog 2014 Dec 13;53(12):939-50. Epub 2013 Jun 13.

Department of Biochemistry and Molecular Biology, University of Las Palmas de Gran Canaria, Las Palmas de Gran Canaria, Spain; Instituto Canario de Investigación del Cáncer, Las Palmas de Gran Canaria, Spain.

Flavonoids are naturally occurring polyphenolic compounds which display a vast array of biological activities. In this study, we investigated the effects of tamarixetin on viability of human tumor cell lines and found that it was cytotoxic against leukemia cells and in particular P-glycoprotein-overexpressing K562/ADR cells. This compound inhibited proliferation in a concentration- and time-dependent manner, induced apoptosis and blocked cell cycle progression at G2 -M phase. This was associated with the accumulation of cyclin B1, Bub1 and p21(Cip1/Waf-1), changes in the phosphorylation status of cyclin B1, Cdk1, Cdc25C and MPM-2, and inhibition of tubulin polymerization. Moreover, cell death was found to be associated with cytochrome c release and cleavage of caspases and of poly(ADP-ribose) polymerase, and completely abrogated by the free-radical scavenger N-acetyl-L-cysteine. The sensitivity of leukemic cells to tamarixetin suggests that it should be considered for further preclinical and in vivo testing.

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December 2014
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