Palladium (II) complex enhances ROS-dependent apoptotic effects via autophagy inhibition and disruption of multiple signaling pathways in colorectal cancer cells

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dc.authoridEngin Ulukaya / 0000-0003-4875-5472
dc.authoridMerve Erkısa Genel / 0000-0002-3127-742X
dc.authorscopusidEngin Ulukaya / 6602927353
dc.authorscopusidMerve Erkısa Genel / 57126208900
dc.authorwosidEngin Ulukaya / K-5792-2018
dc.authorwosidMerve Erkısa Genel / AAM-1001-2020
dc.contributor.authorAydınlık, Şeyma
dc.contributor.authorErkısa Genel, Merve
dc.contributor.authorArı, Ferda
dc.contributor.authorÇelikler, Serap
dc.contributor.authorUlukaya, Engin
dc.date.accessioned2020-10-02T13:02:16Z
dc.date.available2020-10-02T13:02:16Z
dc.date.issued2021en_US
dc.departmentISU, Rektörlük, Uygulama ve Araştırma Merkezleri, Moleküler Kanser Uygulama ve Araştırma Merkezien_US
dc.description.abstractBackground: Inhibition of autophagy is reported to be a therapeutically effective strategy in overcoming the resistance that is a deadly outcome in cancer. One of the most common reasons for chemo-resistance to treatment is the patients with tumors exhibiting a KRAS mutation which occurs in approximately 40% of colorectal cancer patients. Objective: Hence, we assessed whether a palladium (Pd)(II) complex is a promising anticancer complex, compared to 5-fluorouracil in KRAS wt HT-29 and KRAS mutant HCT-15 cells. Methods: HCT-15 and HT-29 cells were used for colorectal cancer and chloroquine (CQ) was used as an inhibitor of autophagy. In this context, cells were treated with Pd(II) complex and 5-FU in combination with CQ for 48 h and cell viability was measured by SRB assay. Cell death mode was examined with M30 and M65 ELISA assays, annexin V/propidium iodide. Autophagy was determined by acridine orange (AO) staining. Furthermore, the expression of various autophagy and apoptosis related proteins were evaluated with Western blotting.Luminex assay and reactive oxygen species (ROS) level were examined. Results: Cell viability was decreased in a dose dependent matter and CQ enhances cytotoxic effect in Pd(II) and 5-FU treated cells in colorectal cancer cells. Our data showed that inhibition of autophagic flux significantly increase intrinsic apoptosis through the activation of ROS. We showed that combinatorial treatment with CQ induces apoptosis via the caspase-dependent mitochondrial pathway. Luminex analysis revealed that the combination resulted in a down-regulation of a NF-?B/AKT/CREB signaling pathways in both cell line, however, decreased Erk1/2 protein expression was only observed after treated with CQ combination in HCT-15 cells. Conclusion: We suggest that inhibition of autophagy along with Pd(II) and 5-FU treatment has a synergistic effect in KRAS-mutant colorectal cancer cells. Autophagy inhibition by CQ promotes apoptosis via blockade of the NF-?B/AKT/CREB and activation of ROS.en_US
dc.identifier.citationAydinlik, S., Erkisa, M., Ari, F., Celikler, S., & Ulukaya, E. (2020). Palladium (II) Complex Enhances ROS-Dependent Apoptotic Effects via Autophagy Inhibition and Disruption of Multiple Signaling Pathways in Colorectal Cancer Cells. Anti-cancer agents in medicinal chemistryen_US
dc.identifier.doi10.2174/1871520620666200929153804en_US
dc.identifier.pmid32990544en_US
dc.identifier.scopus2-s2.0-85103061725en_US
dc.identifier.scopusqualityN/Aen_US
dc.identifier.urihttps://doi.org/10.2174/1871520620666200929153804
dc.identifier.urihttps://hdl.handle.net/20.500.12713/1128
dc.identifier.wosWOS:000626296300001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.institutionauthorErkısa Genel, Merve
dc.institutionauthorUlukaya, Engin
dc.language.isoenen_US
dc.relation.ispartofAnticancer Agents Med Chemen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectApoptosisen_US
dc.subjectPalladium (II) Complexen_US
dc.subjectROSen_US
dc.subjectAutophagyen_US
dc.subjectColorectal Canceren_US
dc.subjectMetal-Based Compoundsen_US
dc.titlePalladium (II) complex enhances ROS-dependent apoptotic effects via autophagy inhibition and disruption of multiple signaling pathways in colorectal cancer cellsen_US
dc.typeArticleen_US

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