Publication:
Dual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines

dc.contributor.coauthorAbdik, Ezgi Avsar
dc.contributor.coauthorAbdik, Huseyin
dc.contributor.coauthorSahin, Fikrettin
dc.contributor.coauthorBerger, Martin R.
dc.contributor.coauthorKaleagasioglu, Ferda
dc.contributor.departmentGraduate School of Health Sciences
dc.contributor.kuauthorTuran, Duygu
dc.contributor.schoolcollegeinstituteGRADUATE SCHOOL OF HEALTH SCIENCES
dc.date.accessioned2024-11-09T23:14:55Z
dc.date.issued2021
dc.description.abstractBackground: Cancer cell survival depends on the cross-regulation between apoptosis and autophagy which share common signaling pathways including PI3K/Akt/mTOR and Bcl-2. The aim of this study was to elucidate the modulation patterns between apoptosis and autophagy following dual inhibition by Akt inhibitor erufosine and Bcl-2 inhibitor ABT-737 in castration-resistant prostate cancer (CRPC) cell lines, PC-3 (Bax+) and DU-145 (Bax-). Methods and Results: Cell cycle progression, apoptotic and autophagic signaling were examined by flow cytometry, multi-caspase assay, Hoechst staining, acridine orange staining of acidic vesicular organelles (AVOs), qRT-PCR and Western Blot. Dual inhibition increased G2/M arrest in PC-3 and DU-145, but not in the healthy prostate epithelium cells, PNT-1A. Only in PC-3, dual inhibition induced synergistic apoptotic and additive autophagic effects. In DU-145 and PNT-1A cells, ABT-737 did not display any remarkable effect on multicaspase activity and erufosine and ABT-737, neither alone nor in combination induced AVOs. By dual inhibition, AKT, BCL-2 and NF-kappa B gene expressions were downregulated in PC-3, both ATG-5 and BECLIN-1 gene expressions were upregulated in DU-145 but Beclin-1 protein expression was substantially reduced in both CRPC cells. Dual inhibition-induced synergistic multicaspase activation in PC-3 degrades and disrupts autophagic activity of Beclin-1, enhancing caspase-dependent apoptosis. However, in DU-145, following dual inhibition, rate of multicaspase induction and apoptosis are lower but autophagy is completely abolished despite markedly increased BECLIN-1 gene expression. Conclusion: In conclusion, antineoplastic drug combinations may display cell-type specific modulation of apoptotic and autophagic signaling and lack of protective autophagy may not necessarily indicate increased chemotherapeutic sensitivity in heterogenous tumor subpopulations.
dc.description.indexedbyWOS
dc.description.indexedbyScopus
dc.description.indexedbyPubMed
dc.description.issue12
dc.description.openaccessNO
dc.description.publisherscopeInternational
dc.description.sponsoredbyTubitakEuN/A
dc.description.sponsorshipScientific and Technological Research Council of Turkey (TUBITAK) [315S039] This study was funded by the Scientific and Technological Research Council of Turkey (TUBITAK), Project No: 315S039.
dc.description.volume48
dc.identifier.doi10.1007/s11033-021-06786-z
dc.identifier.eissn1573-4978
dc.identifier.issn0301-4851
dc.identifier.quartileQ3
dc.identifier.scopus2-s2.0-85116875248
dc.identifier.urihttps://doi.org/10.1007/s11033-021-06786-z
dc.identifier.urihttps://hdl.handle.net/20.500.14288/10242
dc.identifier.wos706928900009
dc.keywordsApoptosis
dc.keywordsAutophagy
dc.keywordsAbt-737
dc.keywordsErufosine
dc.keywordsCastration-resistant prostate cancer myelogenous leukemia-cells
dc.keywordsErufosine
dc.keywordsAbt-737
dc.keywordsAlkylphosphocholine
dc.keywordsCombination
dc.keywordsExpression
dc.keywordsCrosstalk
dc.keywordsDocetaxel
dc.language.isoeng
dc.publisherSpringer
dc.relation.ispartofMolecular Biology Reports
dc.subjectBiochemistry
dc.subjectMolecular biology
dc.titleDual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines
dc.typeJournal Article
dspace.entity.typePublication
local.contributor.kuauthorTuran, Duygu
local.publication.orgunit1GRADUATE SCHOOL OF HEALTH SCIENCES
local.publication.orgunit2Graduate School of Health Sciences
relation.isOrgUnitOfPublication2f870f28-12c9-4b28-9465-b91a69c1d48c
relation.isOrgUnitOfPublication.latestForDiscovery2f870f28-12c9-4b28-9465-b91a69c1d48c
relation.isParentOrgUnitOfPublication4c75e0a5-ca7f-4443-bd78-1b473d4f6743
relation.isParentOrgUnitOfPublication.latestForDiscovery4c75e0a5-ca7f-4443-bd78-1b473d4f6743

Files