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Induction of G 2 /M phase arrest and apoptosis by the flavonoid tamarixetin on human leukemia cells
Author(s) -
Nicolini Fabio,
Burmistrova Olga,
Marrero María Teresa,
Torres Fernando,
Hernández Cristina,
Quintana José,
Estévez Francisco
Publication year - 2014
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.22055
Subject(s) - biology , apoptosis , cyclin b1 , cyclin dependent kinase 1 , cytotoxic t cell , cell cycle , microbiology and biotechnology , programmed cell death , poly adp ribose polymerase , cell cycle checkpoint , biochemistry , cancer research , in vitro , polymerase , enzyme
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 G 2 ‐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. © 2013 Wiley Periodicals, Inc.