Flavonoid quercetin, but not apigenin or luteolin, induced apoptosis in human myeloid leukemia cells and their resistant variants.
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.
Duraj
J
J
Cancer Research Institute, Slovak Academy of Sciences, 833 91 Bratislava, Slovak Republic. exondura@savba.sk
Zazrivcova
K
K
Bodo
J
J
Sulikova
M
M
Sedlak
J
J
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018797:Cell Cycle Proteins / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004249:DNA Damage; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D018922:HL-60 Cells; D006801:Humans; D047311:Luteolin / Q000494:pharmacology*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D011794:Quercetin / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; C493956:CDKN1A protein, human; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D011518:Proto-Oncogene Proteins; D047310:Apigenin; D004317:Doxorubicin; D011794:Quercetin; C494918:AKT1 protein, human; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D047311:Luteolin