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.coauthor | Abdik, Ezgi Avsar | |
dc.contributor.coauthor | Abdik, Huseyin | |
dc.contributor.coauthor | Sahin, Fikrettin | |
dc.contributor.coauthor | Berger, Martin R. | |
dc.contributor.coauthor | Kaleagasioglu, Ferda | |
dc.contributor.department | Graduate School of Health Sciences | |
dc.contributor.kuauthor | Turan, Duygu | |
dc.contributor.schoolcollegeinstitute | GRADUATE SCHOOL OF HEALTH SCIENCES | |
dc.date.accessioned | 2024-11-09T23:14:55Z | |
dc.date.issued | 2021 | |
dc.description.abstract | Background: 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.indexedby | WOS | |
dc.description.indexedby | Scopus | |
dc.description.indexedby | PubMed | |
dc.description.issue | 12 | |
dc.description.openaccess | NO | |
dc.description.publisherscope | International | |
dc.description.sponsoredbyTubitakEu | N/A | |
dc.description.sponsorship | Scientific 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.volume | 48 | |
dc.identifier.doi | 10.1007/s11033-021-06786-z | |
dc.identifier.eissn | 1573-4978 | |
dc.identifier.issn | 0301-4851 | |
dc.identifier.quartile | Q3 | |
dc.identifier.scopus | 2-s2.0-85116875248 | |
dc.identifier.uri | https://doi.org/10.1007/s11033-021-06786-z | |
dc.identifier.uri | https://hdl.handle.net/20.500.14288/10242 | |
dc.identifier.wos | 706928900009 | |
dc.keywords | Apoptosis | |
dc.keywords | Autophagy | |
dc.keywords | Abt-737 | |
dc.keywords | Erufosine | |
dc.keywords | Castration-resistant prostate cancer myelogenous leukemia-cells | |
dc.keywords | Erufosine | |
dc.keywords | Abt-737 | |
dc.keywords | Alkylphosphocholine | |
dc.keywords | Combination | |
dc.keywords | Expression | |
dc.keywords | Crosstalk | |
dc.keywords | Docetaxel | |
dc.language.iso | eng | |
dc.publisher | Springer | |
dc.relation.ispartof | Molecular Biology Reports | |
dc.subject | Biochemistry | |
dc.subject | Molecular biology | |
dc.title | Dual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines | |
dc.type | Journal Article | |
dspace.entity.type | Publication | |
local.contributor.kuauthor | Turan, Duygu | |
local.publication.orgunit1 | GRADUATE SCHOOL OF HEALTH SCIENCES | |
local.publication.orgunit2 | Graduate School of Health Sciences | |
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