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Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species

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Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species

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dc.contributor.author Papież, Monika A. [SAP20001370] pl
dc.contributor.author Krzyściak, Wirginia [SAP20002377] pl
dc.contributor.author Szade, Krzysztof [SAP14008846] pl
dc.contributor.author Bukowska-Straková, Karolina [SAP20002639] pl
dc.contributor.author Kozakowska, Magdalena [SAP14011348] pl
dc.contributor.author Hajduk, Karolina [SAP14010921] pl
dc.contributor.author Bystrowska, Beata [SAP20001721] pl
dc.contributor.author Dulak, Józef [SAP11012135] pl
dc.contributor.author Józkowicz, Alicja [SAP11114690] pl
dc.date.accessioned 2016-04-06T11:51:00Z
dc.date.available 2016-04-06T11:51:00Z
dc.date.issued 2016 pl
dc.identifier.uri http://ruj.uj.edu.pl/xmlui/handle/item/23509
dc.language eng pl
dc.rights Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne 3.0 *
dc.rights.uri http://creativecommons.org/licenses/by-nc/3.0/legalcode *
dc.title Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species pl
dc.type JournalArticle pl
dc.description.physical 557-570 pl
dc.description.additional pl
dc.abstract.en Curcumin may exert a more selective cytotoxic effect in tumor cells with elevated levels of free radicals. Here, we investigated whether curcumin can modulate etoposide action in myeloid leukemia cells and in normal cells of hematopoietic origin. HL-60 cell line, normal myeloid progenitor cluster of differentiation (CD)-34+ cells, and granulocytes were incubated for 4 or 24 hours at different concentrations of curcumin and/or etoposide. Brown Norway rats with acute myeloid leukemia (BNML) were used to prove the influence of curcumin on etoposide action in vivo. Rats were treated with curcumin for 23 days and etoposide was administered for the final 3 days of the experiment. Curcumin synergistically potentiated the cytotoxic effect of etoposide, and it intensified apoptosis and phosphorylation of the histone H2AX induced by this cytostatic drug in leukemic HL-60 cells. In contrast, curcumin did not significantly modify etoposide-induced cytotoxicity and H2AX phosphorylation in normal CD34+ cells and granulocytes. Curcumin modified the cytotoxic action of etoposide in HL-60 cells through intensification of free radical production because preincubation with N-acetyl-l-cysteine (NAC) significantly reduced the cytotoxic effect of curcumin itself and a combination of two compounds. In contrast, NAC did not decrease the cytotoxic effect of etoposide. Thus, oxidative stress plays a greater role in the cytotoxic effect of curcumin than that of etoposide in HL-60 cells. In vitro results were confirmed in a BNML model. Pretreatment with curcumin enhanced the antileukemic activity of etoposide in BNML rats (1.57-fold tumor reduction versus etoposide alone; P<0.05) and induced apoptosis of BNML cells more efficiently than etoposide alone (1.54-fold change versus etoposide alone; P<0.05), but this treatment protected nonleukemic B-cells from apoptosis. Thus, curcumin can increase the antileukemic effect of etoposide through reactive oxygen species in sensitive myeloid leukemia cells, and it is harmless to normal human cells. pl
dc.subject.en acute myeloid leukemia pl
dc.subject.en curcumin pl
dc.subject.en etoposide pl
dc.subject.en ROS pl
dc.subject.en γ-H2AX pl
dc.subject.en apoptosis pl
dc.description.volume 10 pl
dc.identifier.doi 10.2147/DDDT.S92687 pl
dc.identifier.eissn 1177-8881 pl
dc.title.journal Drug Design Development and Therapy pl
dc.language.container eng pl
dc.affiliation Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Biotechnologii Medycznej pl
dc.affiliation Wydział Farmaceutyczny : Katedra Toksykologii pl
dc.affiliation Wydział Lekarski : Instytut Pediatrii pl
dc.affiliation Wydział Farmaceutyczny : Zakład Diagnostyki Medycznej pl
dc.affiliation Wydział Farmaceutyczny : Zakład Cytobiologii pl
dc.subtype Article pl
dc.rights.original CC-BY-NC; otwarte czasopismo; ostateczna wersja wydawcy; w momencie opublikowania; 0; pl
dc.identifier.project ROD UJ / P pl
.pointsMNiSW [2016 A]: 30


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Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne 3.0 Except where otherwise noted, this item's license is described as Udzielam licencji. Uznanie autorstwa - Użycie niekomercyjne 3.0