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dc.contributor.authorAbdik, Huseyin
dc.contributor.authorTuran, Duygu
dc.contributor.authorSahin, Fikrettin
dc.contributor.authorBerger, Martin R.
dc.contributor.authorKaleagasioglu, Ferda
dc.contributor.authorAbdik, EZGİ
dc.date.accessioned2023-10-10T13:05:46Z
dc.date.available2023-10-10T13:05:46Z
dc.date.issued2021
dc.identifier.citationAbdik E., Abdik H., Turan D., Sahin F., Berger M. R., Kaleagasioglu F., "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, cilt.48, sa.12, ss.7755-7765, 2021
dc.identifier.issn0301-4851
dc.identifier.othervv_1032021
dc.identifier.otherav_2bb644c9-3fab-408b-9e72-b9b452a3a0ec
dc.identifier.urihttp://hdl.handle.net/20.500.12627/190429
dc.identifier.urihttps://doi.org/10.1007/s11033-021-06786-z
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.language.isoeng
dc.subjectGenel Biyokimya, Genetik ve Moleküler Biyoloji
dc.subjectSitogenetik
dc.subjectBİYOKİMYA VE MOLEKÜLER BİYOLOJİ
dc.subjectMoleküler Biyoloji ve Genetik
dc.subjectYaşam Bilimleri (LIFE)
dc.subjectYaşam Bilimleri
dc.subjectTemel Bilimler
dc.subjectİlaç Keşfi
dc.subjectYapısal Biyoloji
dc.subjectMoleküler Biyoloji
dc.subjectKlinik Biyokimya
dc.subjectKanser Araştırmaları
dc.subjectBiyokimya
dc.subjectYaşlanma
dc.subjectBiyokimya, Genetik ve Moleküler Biyoloji (çeşitli)
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.typeMakale
dc.relation.journalMOLECULAR BIOLOGY REPORTS
dc.contributor.departmentYeditepe Üniversitesi , ,
dc.identifier.volume48
dc.identifier.issue12
dc.identifier.startpage7755
dc.identifier.endpage7765
dc.contributor.firstauthorID4560139


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