TY - JOUR
T1 - Induction of G2/M phase arrest and apoptosis by the flavonoid tamarixetin on human leukemia cells
AU - Nicolini, Fabio
AU - Burmistrova, Olga
AU - Marrero, María Teresa
AU - Torres, Fernando
AU - Hernández, Cristina
AU - Quintana, José
AU - Estévez, Francisco
PY - 2014/12/1
Y1 - 2014/12/1
N2 - 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 p21Cip1/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.
AB - 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 p21Cip1/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.
KW - Apoptosis
KW - Cell cycle arrest
KW - Flavonoids
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U2 - 10.1002/mc.22055
DO - 10.1002/mc.22055
M3 - Article
C2 - 23765509
AN - SCOPUS:84911420590
VL - 53
SP - 939
EP - 950
JO - Molecular Carcinogenesis
JF - Molecular Carcinogenesis
SN - 0899-1987
IS - 12
ER -