Combination of ERK2 inhibitor VX-11e and voreloxin synergistically enhances anti-proliferative and pro-apoptotic effects in leukemia cells

2019
journal article
article
11
dc.abstract.enERK1/2 inhibitors are new promising anticancer drugs. The aim of this study was to investigate the effect of the combination of ERK2 inhibitor VX-11e and voreloxin on MOLM-14, K562, REH and MOLT-4 leukemia cell lines. We found that VX-11e alone and in combination with voreloxin significantly decreased ERK activation in all cell lines tested. To evaluate the interactions of the drugs, cells were treated for 24 h with VX-11e or voreloxin alone and in combination at fixed ratios based on IC50 values. The combinatorial effects of both drugs were synergistic over a wide range of concentrations in MOLM-14, REH and MOLT-4 cell lines. In K562 cells, three effects were found to be additive, one antagonistic and only one synergistic. The results showed that incubation with both VX-11e and voreloxin inhibited the growth of leukemia cells, affected cell cycle and induced apoptosis. Furthermore, the molecular mechanism of these effects might be attributed to an increased expression of p21 and a decreased expression of survivin and NF-κB in all cell lines tested except from K562 cells. In conclusion, combination of VX-11e and voreloxin can exert a synergistic anticancer effect in leukemia cells.pl
dc.affiliationWydział Lekarski : Zakład Biochemii Ogólnejpl
dc.affiliationWydział Lekarski : Zakład Histologiipl
dc.cm.date2020-12-02
dc.cm.id96133
dc.contributor.authorJasek-Gajda, Ewa - 159982 pl
dc.contributor.authorJurkowska, Halina - 129930 pl
dc.contributor.authorJasińska, Małgorzata - 199998 pl
dc.contributor.authorLitwin, Jan - 130699 pl
dc.contributor.authorLis, Grzegorz - 130689 pl
dc.date.accession2020-07-07pl
dc.date.accessioned2020-12-02T10:07:41Zpl
dc.date.available2020-12-02T10:07:41Zpl
dc.date.issued2019pl
dc.date.openaccess0
dc.description.accesstimew momencie opublikowania
dc.description.number11-12pl
dc.description.physical849-861pl
dc.description.points100pl
dc.description.versionostateczna wersja wydawcy
dc.description.volume24pl
dc.identifier.doi10.1007/s10495-019-01564-6pl
dc.identifier.eissn1573-675Xpl
dc.identifier.issn1360-8185pl
dc.identifier.projectROD UJ / OPpl
dc.identifier.urihttps://ruj.uj.edu.pl/xmlui/handle/item/256141
dc.identifier.weblinkhttps://link.springer.com/article/10.1007%2Fs10495-019-01564-6pl
dc.languageengpl
dc.language.containerengpl
dc.rightsUdzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa*
dc.rights.licenceCC-BY
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcode.pl*
dc.share.typeinne
dc.subject.enVX-11epl
dc.subject.envoreloxinpl
dc.subject.enleukemia cell linespl
dc.subject.enapoptosispl
dc.subject.encell cyclepl
dc.subtypeArticlepl
dc.titleCombination of ERK2 inhibitor VX-11e and voreloxin synergistically enhances anti-proliferative and pro-apoptotic effects in leukemia cellspl
dc.title.journalApoptosispl
dc.typeJournalArticlepl
dspace.entity.typePublication
dc.abstract.enpl
ERK1/2 inhibitors are new promising anticancer drugs. The aim of this study was to investigate the effect of the combination of ERK2 inhibitor VX-11e and voreloxin on MOLM-14, K562, REH and MOLT-4 leukemia cell lines. We found that VX-11e alone and in combination with voreloxin significantly decreased ERK activation in all cell lines tested. To evaluate the interactions of the drugs, cells were treated for 24 h with VX-11e or voreloxin alone and in combination at fixed ratios based on IC50 values. The combinatorial effects of both drugs were synergistic over a wide range of concentrations in MOLM-14, REH and MOLT-4 cell lines. In K562 cells, three effects were found to be additive, one antagonistic and only one synergistic. The results showed that incubation with both VX-11e and voreloxin inhibited the growth of leukemia cells, affected cell cycle and induced apoptosis. Furthermore, the molecular mechanism of these effects might be attributed to an increased expression of p21 and a decreased expression of survivin and NF-κB in all cell lines tested except from K562 cells. In conclusion, combination of VX-11e and voreloxin can exert a synergistic anticancer effect in leukemia cells.
dc.affiliationpl
Wydział Lekarski : Zakład Biochemii Ogólnej
dc.affiliationpl
Wydział Lekarski : Zakład Histologii
dc.cm.date
2020-12-02
dc.cm.id
96133
dc.contributor.authorpl
Jasek-Gajda, Ewa - 159982
dc.contributor.authorpl
Jurkowska, Halina - 129930
dc.contributor.authorpl
Jasińska, Małgorzata - 199998
dc.contributor.authorpl
Litwin, Jan - 130699
dc.contributor.authorpl
Lis, Grzegorz - 130689
dc.date.accessionpl
2020-07-07
dc.date.accessionedpl
2020-12-02T10:07:41Z
dc.date.availablepl
2020-12-02T10:07:41Z
dc.date.issuedpl
2019
dc.date.openaccess
0
dc.description.accesstime
w momencie opublikowania
dc.description.numberpl
11-12
dc.description.physicalpl
849-861
dc.description.pointspl
100
dc.description.version
ostateczna wersja wydawcy
dc.description.volumepl
24
dc.identifier.doipl
10.1007/s10495-019-01564-6
dc.identifier.eissnpl
1573-675X
dc.identifier.issnpl
1360-8185
dc.identifier.projectpl
ROD UJ / OP
dc.identifier.uri
https://ruj.uj.edu.pl/xmlui/handle/item/256141
dc.identifier.weblinkpl
https://link.springer.com/article/10.1007%2Fs10495-019-01564-6
dc.languagepl
eng
dc.language.containerpl
eng
dc.rights*
Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa
dc.rights.licence
CC-BY
dc.rights.uri*
http://creativecommons.org/licenses/by/4.0/legalcode.pl
dc.share.type
inne
dc.subject.enpl
VX-11e
dc.subject.enpl
voreloxin
dc.subject.enpl
leukemia cell lines
dc.subject.enpl
apoptosis
dc.subject.enpl
cell cycle
dc.subtypepl
Article
dc.titlepl
Combination of ERK2 inhibitor VX-11e and voreloxin synergistically enhances anti-proliferative and pro-apoptotic effects in leukemia cells
dc.title.journalpl
Apoptosis
dc.typepl
JournalArticle
dspace.entity.type
Publication
Affiliations

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