Origanum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cells

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dc.authoridBiray Avcı, Cigir/0000-0001-8251-4520
dc.authoridKayalar, Hüsniye/0000-0001-7882-0517
dc.authoridGunduz, Cumhur/0000-0002-6593-3237
dc.authorwosidBiray Avcı, Cigir/GWV-1665-2022
dc.authorwosidKayalar, Hüsniye/AAZ-4012-2021
dc.authorwosidGunduz, Cumhur/GOP-0629-2022
dc.contributor.authorKayabasi, Cagla
dc.contributor.authorYilmaz Susluer, Sunde
dc.contributor.authorBalci Okcanoglu, Tugce
dc.contributor.authorOzmen Yelken, Besra
dc.contributor.authorMutlu, Zeynep
dc.contributor.authorGoker Bagca, Bakiye
dc.contributor.authorCaliskan Kurt, Cansu
dc.date.accessioned2023-03-22T19:47:32Z
dc.date.available2023-03-22T19:47:32Z
dc.date.issued2022
dc.departmentBelirleneceken_US
dc.description.abstractOriganum sipyleum is used in folk medicine due to its anti-inflammatory, antimicrobial, and antioxidant properties. Ponatinib, an effective tyrosine kinase inhibitor in the treatment of chronic myeloid leukemia (CML), has severe side effects. Thus, we aimed to determine a novel herbal combination therapy that might not only increase the anti-leukemic efficacy but also reduce the dose of ponatinib in targeting CML cells. Origanum sipyleum was extracted with methanol (OSM), and secondary metabolites were determined by phytochemical screening tests. The cytotoxic effects of OSM on K562 cells were measured by WST-1 assay. Median-effect equation was used to analyze the combination of ponatinib and OSM (p-OSM). Apoptosis, proliferation, and cell-cycle were investigated by flow-cytometry. Cell-cycle-related gene expressions were evaluated by qRT-PCR. OSM that contains terpenoids, flavonoids, tannins, and anthracenes exhibited cytotoxic effects on K562 cells. The median-effect of p-OSM was found as synergistic; OSM reduced the ponatinib dose similar to 5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G(0)/G(1), S phases accompanied by regulations in TGFB2, ATR, PP2A, p18, CCND1, CCND2, and CCNA1 expressions. OSM enhanced the anti-leukemic activity of ponatinib synergistically via inducing apoptosis, suppressing proliferation, and cell-cycle. As a result, OSM might offer a potential strategy for treating patients with CML.en_US
dc.description.sponsorship[110S289]en_US
dc.description.sponsorshipThe Origanum sipyleum L. methanol extract was obtained from TuBTAK project no 110S289. We thank Ege University School of Foreign Languages and Lecturer Dr. Atiyye Hilal SENGENC for providing professional English editing for this manuscript.en_US
dc.identifier.doi10.1080/01635581.2022.2077969
dc.identifier.endpage3691en_US
dc.identifier.issn0163-5581
dc.identifier.issn1532-7914
dc.identifier.issue10en_US
dc.identifier.pmid35608652en_US
dc.identifier.scopus2-s2.0-85131012611en_US
dc.identifier.scopusqualityQ2en_US
dc.identifier.startpage3679en_US
dc.identifier.urihttps://doi.org/10.1080/01635581.2022.2077969
dc.identifier.urihttps://hdl.handle.net/20.500.14034/758
dc.identifier.volume74en_US
dc.identifier.wosWOS:000801179300001en_US
dc.identifier.wosqualityQ3en_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherRoutledge Journals, Taylor & Francis Ltden_US
dc.relation.journalNutrition And Cancer-An International Journalen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectBiologyen_US
dc.subjectDifferentiationen_US
dc.subjectMechanismsen_US
dc.subjectResistanceen_US
dc.subjectPathwaysen_US
dc.subjectDiseaseen_US
dc.subjectBcr/Ablen_US
dc.subjectPp2aen_US
dc.subjectCmlen_US
dc.titleOriganum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cellsen_US
dc.typeArticleen_US

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