dc.contributor.author | Nalkıran, Hatice Sevim | |
dc.contributor.author | Yıldız, Dilara Akcora | |
dc.contributor.author | Saydam, Faruk | |
dc.contributor.author | Güzel, Ali İrfan | |
dc.contributor.author | Nalkıran, İhsan | |
dc.date.accessioned | 2023-08-23T06:11:16Z | |
dc.date.available | 2023-08-23T06:11:16Z | |
dc.date.issued | 2023 | en_US |
dc.identifier.citation | Sevim Nalkiran, H., Akcora Yildiz, D., Saydam, F., Guzel, A. I., & Nalkiran, I. (2023). Targeting the anaphase-promoting complex/cyclosome (APC/C) enhanced antiproliferative and apoptotic response in bladder cancer. Saudi journal of biological sciences, 30(3), 103564. https://doi.org/10.1016/j.sjbs.2023.103564 | en_US |
dc.identifier.issn | 2213-7106 | |
dc.identifier.issn | 1319-562X | |
dc.identifier.uri | https://doi.org/10.1016/j.sjbs.2023.103564 | |
dc.identifier.uri | https://hdl.handle.net/11436/8107 | |
dc.description.abstract | Improving the chemotherapy sensitivity of bladder cancer is a current clinical challenge. It is critical to seek out effective combination therapies that include low doses of cisplatin due to its dose-limiting toxicity. This study aims to investigate the cytotoxic effects of the combination therapy including proTAME, a small molecule inhibitor, targeting Cdc-20 and to determine the expression levels of several APC/C pathway-related genes that may play a role in the chemotherapy response of RT-4 (bladder cancer) and ARPE-19 (normal epithelial) cells. The IC20 and IC50 values were determined by MTS assay. The expression levels of apoptosis-associated (Bax and Bcl-2) and APC/C-associated (Cdc-20, Cyclin-B1, Securin, and Cdh-1) genes were assessed by qRT-PCR. Cell colonization ability and apoptosis were examined by clonogenic survival experiment and Annexin V/PI staining, respectively. Low-dose combination therapy showed a superior inhibition effect on RT-4 cells by increasing cell death and inhibiting colony formation. Triple-agent combination therapy further increased the percentage of late apoptotic and necrotic cells compared to the doublet-therapy with gemcitabine and cisplatin. ProTAME-containing combination therapies resulted in an elevation in Bax/Bcl-2 ratio in RT-4 cells, while a significant decrease was observed in proTAME-treated ARPE-19 cells. Cdc-20 expression in proTAME combined treatment groups were found to be decreased compared to their control groups. Low-dose triple-agent combination induced cytotoxicity and apoptosis in RT-4 cells effectively. It is essential to evaluate the role of APC/C pathway-associated potential biomarkers as therapeutic targets and define new combination therapy regimens to achieve improved tolerability in bladder cancer patients in the future. | en_US |
dc.language.iso | eng | en_US |
dc.publisher | Elsevier | en_US |
dc.rights | info:eu-repo/semantics/openAccess | en_US |
dc.subject | Bladder cancer | en_US |
dc.subject | Small-molecule inhibitor | en_US |
dc.subject | ProTAME Cisplatin | en_US |
dc.subject | Gemcitabine | en_US |
dc.subject | Apoptosis | en_US |
dc.title | Targeting the anaphase-promoting complex/cyclosome (APC/C) enhanced antiproliferative and apoptotic response in bladder cancer | en_US |
dc.type | article | en_US |
dc.contributor.department | RTEÜ, Tıp Fakültesi, Temel Tıp Bilimleri Bölümü | en_US |
dc.contributor.institutionauthor | Nalkıran, Hatice Sevim | |
dc.contributor.institutionauthor | Saydam, Faruk | |
dc.contributor.institutionauthor | Nalkıran, İhsan | |
dc.identifier.doi | 10.1016/j.sjbs.2023.103564 | en_US |
dc.identifier.volume | 30 | en_US |
dc.identifier.issue | 3 | en_US |
dc.identifier.startpage | 103564 | en_US |
dc.relation.journal | Saudi Journal of Biological Sciences | en_US |
dc.relation.publicationcategory | Makale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı | en_US |