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Induction of apoptosis by quercetin: different response of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells

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Abstract

This work shows that 25 μM 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 G2/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.

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Abbreviations

Ac-DEVD-AMC:

Acetyl-Asp-Glu-Val-Asp-aminomethylcoumarin

BSO:

buthionine-l-sulphoximine

DCFH-DA:

2′,7′-dichlorofluorescein diacetate

DEM:

diethyl maleate

ECL:

enhanced chemiluminescence

NAC:

N-acetyl-l-cysteine

ROS:

reactive oxygen species

t-BHP:

tert-butylhydroperoxide

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Acknowledgment

This work was partially supported by the “Ministero dell’Università e della Ricerca Scientifica” (PRIN 2004) to AB.

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Authors and Affiliations

  1. Department of Biochemical Sciences and Technologies, University of L’Aquila, Via Vetoio, Coppito 2, 67100, L’Aquila, Italy

    Fabrizia Brisdelli, Cristina Coccia & Argante Bozzi

  2. Department of Experimental Medicine, University of L’Aquila, Via Vetoio, Coppito 2, 67100, L’Aquila, Italy

    Benedetta Cinque & Maria Grazia Cifone

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  1. Fabrizia Brisdelli
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  2. Cristina Coccia
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  3. Benedetta Cinque
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  4. Maria Grazia Cifone
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  5. Argante Bozzi
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Correspondence to Argante Bozzi.

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Brisdelli, F., Coccia, C., Cinque, B. et al. Induction of apoptosis by quercetin: different response of human chronic myeloid (K562) and acute lymphoblastic (HSB-2) leukemia cells. Mol Cell Biochem 296, 137–149 (2007). https://doi.org/10.1007/s11010-006-9307-3

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