Vacuolar-ATPase-mediated intracellular sequestration of ellipticine contributes to drug resistance in neuroblastoma cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11130%2F15%3A10306941" target="_blank" >RIV/00216208:11130/15:10306941 - isvavai.cz</a>

Alternative codes found

RIV/62156489:43210/15:43907633 RIV/00216208:11310/15:10306941 RIV/00216305:26620/15:PU118468 RIV/00064203:_____/15:10306941

Result on the web

<a href="http://dx.doi.org/10.3892/ijo.2015.3066" target="_blank" >http://dx.doi.org/10.3892/ijo.2015.3066</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.3892/ijo.2015.3066" target="_blank" >10.3892/ijo.2015.3066</a>

Result language

angličtina

Original language name

Vacuolar-ATPase-mediated intracellular sequestration of ellipticine contributes to drug resistance in neuroblastoma cells

Original language description

Neuroblastoma is the most common cancer in infants and the fourth most common cancer in children. Aggressive cell growth and chemoresistance are notorious obstacles in neuroblastoma therapy. Exposure to the anticancer drug ellipticine inhibits efficiently growth of neuroblastoma cells and induces apoptosis in these cells. However, ellipticine induced resistance in these cells. The upregulation of a vacuolar (V)-ATPase gene is one of the factors associated with resistance development. In accordance with this finding, we found that levels of V-ATPase protein expression are higher in the ellipticine-resistant UKF-NB-4(ELLI) line than in the parental ellipticine-sensitive UKF-NB-4 cell line. Treatment of ellipticine-sensitive UKF-NB-4 and ellipticine-resistant UKF-NB-4(ELLI) cells with ellipticine-induced cytoplasmic vacuolization and ellipticine is concentrated in these vacuoles. Confocal microscopy and staining of the cells with a lysosomal marker suggested these vacuoles as lysosomes. Transmission electron microscopy and no effect of an autophagy inhibitor wortmannin ruled out autophagy. Pretreatment with a V-ATPase inhibitor bafilomycin A and/or the lysosomotropic drug chloroquine prior to ellipticine enhanced the ellipticine-mediated apoptosis and decreased ellipticine-resistance in UKF-NB-4(ELLI) cells. Moreover, pretreatment with these inhibitors increased formation of ellipticine-derived DNA adducts, one of the most important DNA-damaging mechanisms responsible for ellipticine cytotoxicity. In conclusion, resistance to ellipticine in the tested neuroblastoma cells is associated with V-ATPase-mediated vacuolar trapping of this drug, which may be decreased by bafilomycin A and/or chloroquine.

Czech name

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Czech description

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Type

J_x - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)

CEP classification

CE - Biochemistry

OECD FORD branch

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Project

Result was created during the realization of more than one project. More information in the Projects tab.

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2015

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

International Journal of Oncology

ISSN

1019-6439

e-ISSN

—

Volume of the periodical

47

Issue of the periodical within the volume

3

Country of publishing house

GR - GREECE

Number of pages

10

Pages from-to

971-980

UT code for WoS article

000359279200019

EID of the result in the Scopus database

2-s2.0-84938080027