Dual akt and bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines

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dc.authoridFerda Kaleağasıoğlu / 0000-0003-1511-0432
dc.authorscopusidFerda Kaleağasıoğlu / 6603420924en_US
dc.authorwosidFerda Kaleağasıoğlu / E-9447-2011
dc.contributor.authorAvşar Abdik, Ezgi
dc.contributor.authorAbdik, Hüseyin
dc.contributor.authorTuran, Duygu
dc.contributor.authorŞahin, Fikrettin
dc.contributor.authorBerger, Martin Reinhold
dc.contributor.authorKaleağasıoğlu, Ferda
dc.date.accessioned2021-10-25T06:18:33Z
dc.date.available2021-10-25T06:18:33Z
dc.date.issued2021en_US
dc.departmentİstinye Üniversitesi, Tıp Fakültesi, Dahili Tıp Bilimleri Bölümüen_US
dc.description.abstractCancer 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-?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. © 2021, The Author(s), under exclusive licence to Springer Nature B.V.en_US
dc.identifier.citationAvsar Abdik, E., Abdik, H., Turan, D., Sahin, F., Berger, M. R., & Kaleagasioglu, F. (2021). Dual Akt and Bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell lines. Molecular Biology Reports: An International Journal on Molecular and Cellular Biology, 1. https://doi.org/10.1007/s11033-021-06786-zen_US
dc.identifier.doi10.1007/s11033-021-06786-zen_US
dc.identifier.endpage9en_US
dc.identifier.issn0301-4851en_US
dc.identifier.issn1573-4978en_US
dc.identifier.scopus2-s2.0-85116875248en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage1en_US
dc.identifier.urihttps://doi.org/10.1007/s11033-021-06786-z
dc.identifier.urihttps://hdl.handle.net/20.500.12713/2165
dc.identifier.wosWOS:000706928900009en_US
dc.identifier.wosqualityQ4en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorKaleağasıoğlu, Ferda
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofMolecular Biology Reportsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectABT-737en_US
dc.subjectApoptosisen_US
dc.subjectAutophagyen_US
dc.subjectCastration-resistant Prostateen_US
dc.subjectCanceren_US
dc.subjectErufosineen_US
dc.titleDual akt and bcl-2 inhibition induces cell-type specific modulation of apoptotic and autophagic signaling in castration resistant prostate cancer cell linesen_US
dc.typeArticleen_US

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