Prikaz osnovnih podataka o dokumentu

dc.creatorHarhaji-Trajković, Ljubica
dc.creatorArsikin, Katarina
dc.creatorKravić-Stevović, Tamara
dc.creatorPetricevic, Sasa
dc.creatorTovilović-Kovačević, Gordana
dc.creatorPantović, Aleksandar
dc.creatorZogović, Nevena
dc.creatorRistić, Biljana
dc.creatorJanjetović, Kristina
dc.creatorBumbaširević, Vladimir
dc.creatorTrajković, Vladimir
dc.date.accessioned2024-07-31T12:37:12Z
dc.date.available2900-01-01
dc.date.issued2012
dc.identifier.issn0724-8741
dc.identifier.urihttp://radar.ibiss.bg.ac.rs/handle/123456789/6887
dc.description.abstractPurpose To investigate the ability of chloroquine, a lysosomotropic autophagy inhibitor, to enhance the anticancer effect of nutrient deprivation. Methods Serum-deprived U251 glioma, B16 melanoma and L929 fibrosarcoma cells were treated with chloroquine in vitro. Cell viability was measured by crystal violet and MTT assay. Oxidative stress, apoptosis/necrosis and intracellular acidification were analyzed by flow cytometry. Cell morphology was examined by light and electron microscopy. Activation of AMP-activated protein kinase (AMPK) and autophagy were monitored by immunoblotting. RNA interference was used for AMPK and LC3b knockdown. The anticancer efficiency of intraperitoneal chloroquine in calorie restricted mice was assessed using a B16mouse melanoma model. Results Chloroquine rapidly killed serum-starved cancer cells in vitro. This effect was not mimicked by autophagy inhibitors or LC3b shRNA, indicating autophagy-independent mechanism. Chloroquine-induced lysosomal accumulation and oxidative stress, leading tomitochondrial depolarization, caspase activation and mixed apoptotic/necrotic cell death, were prevented by lysosomal acidification inhibitor bafilomycin. AMPK downregulation participated in chloroquine action, as AMPK activation reduced, and AMPK shRNA mimicked chloroquine toxicity. Chloroquine inhibited melanoma growth in calorie-restricted mice, causing lysosomal accumulation, mitochondrial disintegration and selective necrosis of tumor cells. Conclusion Combined treatment with chloroquine and calorie restriction might be useful in cancer therapy.sr
dc.language.isoensr
dc.publisherSpringer Naturesr
dc.relationUnesco L'Oreal za žene u nauci čiji je nosilac bila dr Harhaji-Trajkovic Ljubica broj ugovora 403Fsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/173053/RS//sr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Integrated and Interdisciplinary Research (IIR or III)/41025/RS//sr
dc.rightsrestrictedAccesssr
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcePharmaceutical Researchsr
dc.subjectAMPKsr
dc.subjectautophagysr
dc.subjectcaloric restrictionsr
dc.subjectcancersr
dc.subjectchloroquinesr
dc.titleChloroquine-mediated lysosomal dysfunction enhances the anticancer effect of nutrient deprivation.sr
dc.typearticlesr
dc.rights.licenseBYsr
dc.rights.holder© 2012, Springer Science Business Media, LLCsr
dc.citation.issue8
dc.citation.volume29
dc.identifier.doi10.1007/s11095-012-0753-1
dc.identifier.pmid21871960
dc.identifier.scopus2-s2.0-84864447560
dc.identifier.wos000306547300019
dc.citation.spage2249
dc.citation.epage2263
dc.type.versionpublishedVersionsr
dc.citation.rankaM21


Dokumenti

Thumbnail

Ovaj dokument se pojavljuje u sledećim kolekcijama

Prikaz osnovnih podataka o dokumentu