Neoplasma Vol.52, p.273-279, 2005
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Title: Flavonoid quercetin, but not apigenin or luteolin, induced
apoptosis in human myeloid leukemia cells and their resistant
variants
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Author: J., DURAJ
; K., ZAZRIVCOVA
; J., BODO
; M., SULIKOVA
; J., SEDLAK
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Abstract: Flavonoids and their in vivo metabolites are neuroprotective,
cardioprotective and chemopreventive agents acting as hydrogen-
donating antioxidants or modulators functioning at protein kinase
and lipid signaling pathways. In presented study
treatments of human leukemia cells HL60 and their MDR-1 resistant
subline HL60/VCR by flavonoids apigenin (API), luteolin
(LUT), quercetin (QU) and anticancer drug doxorubicin (DOX) are
reported. Of all flavonoids used only QU treatments
led in both cell lines to DNA fragmentation, cleavage of poly (ADP-
ribose) polymerase (PARP), up-regulation of
proapoptotic Bax and posttranslational modification
(phosphorylation) of antiapoptotic Bcl-2. Cytochrome c and
p21WAF1/CIP1 levels remained unchanged in these cells.
Furthermore, treatments of both cell lines by QU and in its
combined
application with DOX increased phosphorylation of ERK, while Akt-1
and phosphorylated Akt-1 levels were not changed.
All these events resulted in effective induction of apoptosis
associated with down-regulation of P-glycoprotein in resistant
cells. Presented results suggest that in human leukemia cells QU
is a potent regulator of the cell apoptotic program associated
with the modulation of several signaling molecules.
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Keywords: dietary flavonoids, quercetin, human leukemia cells, P-
glycoprotein, apoptosis, flow cytometry, western blotting
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Year: 2005, Volume: 52, Issue: |
Page From: 273, Page To: 279 |
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