The mechanism of anticancer effects of some pyrrolopyrimidine derivatives on HT-29 human colon cancer cells
| dc.authorid | 000-0002-0292-4448 | tr |
| dc.contributor.author | mustafa ergül | |
| dc.contributor.author | zuhal kılıç kurt | |
| dc.contributor.author | yeliz aka | |
| dc.contributor.author | özgür kütük | |
| dc.contributor.author | ZEYNEP DENİZ ŞAHİN İNAN | |
| dc.date.accessioned | 2024-02-29T14:02:13Z | |
| dc.date.available | 2024-02-29T14:02:13Z | |
| dc.date.issued | 2023 | tr |
| dc.department | Tıp Fakültesi | tr |
| dc.description.abstract | In the present work, the mechanism of anticancer activity of some pyrrolopyrimidine derivatives was evaluated. Compounds 5 and 8 exhibiting significant antiproliferative activity against HT-29 cells with IC50 values of 4.17 μM and 2.96, arrested the cells at the G2/M phase and significantly induced apoptosis. The apoptotic potential of the compounds has been verified via ELISA assay, which resulted in increased BAX, PUMA, BIM, and cleaved caspase 3 expression and decreased BCL-XL and MCL-1 protein levels in HT-29 cells. Moreover, the immuno fluorescence technique showing that compounds 5 and 8-treatment reduced Ki67 immunolocalization and increased the caspase 3 and p53 immunolocalization confirmed the apoptotic activity. While treatment of HT-29 cells to compounds 5 and 8 inhibited Akt and ERK1/2, there are no alterations in JNK and p38 signaling pathways. According to molecular docking results, compounds 5 and 8 occupied the active site of Akt kinase and showed important hydrogen bonding interactions with key amino acids. Also, siRNA-mediated depletion of BIM, PUMA, and BAX/BAK expression decreased apoptotic response in HT-29 cells upon exposure to compound 5 and compound 8. Compounds 5 and 8 trigger the activation of mitochondrial apoptosis in HT-29 cells. Additionally, we found that proapoptotic BH3-only proteins BIM and PUMA are required for the full engagement of mito chondrial apoptosis signaling. However, p53 was dispensable for compound 5- or compound 8-induced apoptosis in HT-29 cells. | tr |
| dc.identifier.doi | 10.1016/j.tiv.2023.105757 | en_US |
| dc.identifier.pmid | 38061602 | en_US |
| dc.identifier.scopus | 2-s2.0-85179930297 | en_US |
| dc.identifier.scopusquality | N/A | |
| dc.identifier.uri | https://hdl.handle.net/20.500.12418/14491 | |
| dc.identifier.wos | WOS:001160391100001 | en_US |
| dc.identifier.wosquality | Q3 | |
| dc.indekslendigikaynak | Web of Science | en_US |
| dc.indekslendigikaynak | Scopus | en_US |
| dc.indekslendigikaynak | PubMed | en_US |
| dc.language.iso | en | en_US |
| dc.relation.publicationcategory | Uluslararası Hakemli Dergide Makale - Kurum Öğretim Elemanı | tr |
| dc.rights | info:eu-repo/semantics/openAccess | tr |
| dc.title | The mechanism of anticancer effects of some pyrrolopyrimidine derivatives on HT-29 human colon cancer cells | en_US |
| dc.type | Article | en_US |
