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

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dc.contributor.authorKayabasi C.
dc.contributor.authorYilmaz Susluer S.
dc.contributor.authorBalci Okcanoglu T.
dc.contributor.authorOzmen Yelken B.
dc.contributor.authorMutlu Z.
dc.contributor.authorGoker Bagca B.
dc.contributor.authorCaliskan Kurt C.
dc.contributor.authorSaydam G.
dc.contributor.authorDurmuskahya C.
dc.contributor.authorKayalar H.
dc.contributor.authorOzbilgin A.
dc.contributor.authorBiray Avci C.
dc.contributor.authorGunduz C.
dc.date.accessioned2024-07-22T08:05:09Z
dc.date.available2024-07-22T08:05:09Z
dc.date.issued2022
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 ∼5-fold. p-OSM elevated the apoptotic and anti-proliferative activity of ponatinib. Consistently, p-OSM blocked cell-cycle progression in G0/G1, 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. © 2022 Taylor & Francis Group, LLC.
dc.identifier.DOI-ID10.1080/01635581.2022.2077969
dc.identifier.issn01635581
dc.identifier.urihttp://akademikarsiv.cbu.edu.tr:4000/handle/123456789/13012
dc.language.isoEnglish
dc.publisherTaylor and Francis Ltd.
dc.subjectanthracene derivative
dc.subjectantineoplastic agent
dc.subjectATR protein
dc.subjectcyclin A1
dc.subjectcyclin D1
dc.subjectcyclin D2
dc.subjectflavonoid
dc.subjectmethanol
dc.subjectOriganum sipyleum extract
dc.subjectphytochemical
dc.subjectponatinib
dc.subjectprotein p18
dc.subjecttannin derivative
dc.subjectterpenoid derivative
dc.subjecttransforming growth factor beta2
dc.subjectunclassified drug
dc.subjectantileukemic activity
dc.subjectantineoplastic activity
dc.subjectantiproliferative activity
dc.subjectapoptosis
dc.subjectArticle
dc.subjectcancer combination chemotherapy
dc.subjectcell cycle G0 phase
dc.subjectcell cycle progression
dc.subjectcell proliferation
dc.subjectchronic myeloid leukemia
dc.subjectcontrolled study
dc.subjectcytotoxicity
dc.subjectdrug efficacy
dc.subjectdrug potency
dc.subjectdrug potentiation
dc.subjectflow cytometry
dc.subjectG1 phase cell cycle checkpoint
dc.subjectG2 phase cell cycle checkpoint
dc.subjectgene expression regulation
dc.subjecthuman
dc.subjecthuman cell
dc.subjectK-562 cell line
dc.subjectOriganum
dc.subjectOriganum sipyleum
dc.subjectphytochemistry
dc.subjectreal time polymerase chain reaction
dc.subjectreceptor down regulation
dc.subjectS phase cell cycle checkpoint
dc.subjectsynergistic effect
dc.subjectWST-1 assay
dc.titleOriganum Sipyleum Methanol Extract in Combination with Ponatinib Shows Synergistic anti-Leukemic Activities on Chronic Myeloid Leukemia Cells
dc.typeArticle

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