Induction of apoptosis by quercetin: different response of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells.
This work shows that 25 microM quercetin caused a marked inhibition of K562 cells growth together with a mild cytotoxicity, while HSB-2 cells were practically unaffected. Moreover, quercetin induced caspase-3 and cytochrome c-dependent apoptosis almost exclusively in the former cell line. Exposure of K562 cells to quercetin caused also a significant increase of cells in G(2)/M phase that reached the maximum peak at 24 h (4-fold with respect to the basal value). The major sensitivity exhibited by K562 cells was only in part imputable to their higher glutathione content, as compared to HSB-2 cells, thus confirming previous reports describing the formation of intracellular quercetin-thiol toxic adducts in cells exposed to the flavonoid. In fact, after induction of intracellular glutathione increase we detected in both cell lines a significant rise of apoptotic cells, again more marked in K562 cells. By contrast, glutathione-depleted cells, failed to show a decrease of apoptosis in both cell lines, thus contradicting our previous findings and literature data. Since the yet unresolved question about the anti-oxidant or the pro-oxidant capacity of quercetin, we investigated which of these two properties worked in our experimental model. Interestingly, not only quercetin did not produce reactive oxygen species but also prevented their formation, as observed in cells exposed to the oxidizing agent ter-butylhydroperoxide, acting as an efficient oxygen radicals scavenger. This result indicates that quercetin exhibited, in these cell lines, anti-oxidant more than pro-oxidant ability.
Brisdelli
Fabrizia
F
Department of Biochemical Sciences and Technologies, University of L'Aquila, Via Vetoio, Coppito 2, 67100 L'Aquila, Italy.
Coccia
Cristina
C
Cinque
Benedetta
B
Cifone
Maria Grazia
MG
Bozzi
Argante
A
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects*; D002470:Cell Survival; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D020014:K562 Cells / Q000187:drug effects*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D045304:Cytochromes c; D011794:Quercetin; D020169:Caspases; D005978:Glutathione