Further elucidation of mechanism of resistance to vincristine in myeloid cells: role of hypochlorous acid in degradation of vincristine by myeloperoxidase

Basit Öğe Kaydı
dc.authorscopusid6603697741
dc.authorscopusid7004209687
dc.authorscopusid7006259584
dc.authorscopusid7102641563
dc.authorscopusid7006234945
dc.contributor.authorÖzgen Ü.
dc.contributor.authorSavaşan S.
dc.contributor.authorStout M.
dc.contributor.authorBuck S.
dc.contributor.authorRavindranath Y.
dc.date.accessioned2024-08-04T19:59:32Z
dc.date.available2024-08-04T19:59:32Z
dc.date.issued2000
dc.departmentİnönü Üniversitesien_US
dc.description.abstractInherent resistance of myeloblasts to vincristine (VCR) has been related to the activity of myeloperoxidase (MPO) which can degrade VCR in the presence of hydrogen peroxide (H2O2). We investigated the relationship between VCR degradation and hypochlorous acid (HOCl) generation from the reaction of H2O2 with chlorine (Cl) as catalyzed by MPO. A cell-free system, three human leukemia cell lines (CEM/CCRF, HL-60, U937) and 15 bone marrow samples from children with acute myeloid leukemia (AML) were studied. VCR cytotoxicity was evaluated by MTT assay and by quantitative measurement of apoptosis. In vitro levels of VCR in cell-free systems were measured by high performance liquid chromatography (HPLC), and intracellular HOCl levels by oxidation of 5-thio-2-nitrobenzoic acid with the accompanying decrease in the absorbency at 412 nm. VCR was degraded by increasing concentrations of HOCl in cell-free systems and this activity was inhibited by taurine, which is known to block HOCl activity. This finding was confirmed by the VCR cytotoxicity studies on cell lines. The HOCl-producing myeloblasts from patients were resistant to VCR. In five samples out of eight HOCl was also detected extracellularly. These results suggest that oxidation by HOCl may be the final step in VCR degradation catalyzed by MPO through its action on intracellular H2O2 and Cl.en_US
dc.description.sponsorshipNational Cancer Institute, NCI: U10CA029691; National Cancer Institute, NCI; Pediatric Oncology Group of Ontario, POGOen_US
dc.description.sponsorshipThis work was supported by a grant from Leukemia Research Life Inc., and the Pediatric Oncology Group (NCI CA-29691).en_US
dc.identifier.doi10.1038/sj.leu.2401627
dc.identifier.endpage51en_US
dc.identifier.issn0887-6924
dc.identifier.issue1en_US
dc.identifier.pmid10637476en_US
dc.identifier.scopus2-s2.0-0342614219en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage47en_US
dc.identifier.urihttps://doi.org/10.1038/sj.leu.2401627
dc.identifier.urihttps://hdl.handle.net/11616/90713
dc.identifier.volume14en_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherNature Publishing Groupen_US
dc.relation.ispartofLeukemiaen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/closedAccessen_US
dc.subjectAcute myeloid leukemiaen_US
dc.subjectHypochlorous aciden_US
dc.subjectMyeloperoxidaseen_US
dc.subjectVincristine resistanceen_US
dc.titleFurther elucidation of mechanism of resistance to vincristine in myeloid cells: role of hypochlorous acid in degradation of vincristine by myeloperoxidaseen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

Scopus İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu