Myeloperoxidase is involved in Vincristine resistance in human myeloblastic leukemia

Schlaifer, Daniel; Cooper, Michael R.; Attal, M; Sartor, AO; Trepel, JB; Müller, Claudia I.; Guy, Laurent; Myers, Carolyn M.

doi:10.1007/978-2-8178-0765-2_156

Cited by 5 publications

(8 citation statements)

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“…They demonstrated that MPO is capable of mediating oxidation of VCR in the presence of H 2 O 2 in both cell-free systems and in the MPO-positive human leukemia cell line, HL-60. 1,7 It was reported that sera from patients with AML had increased ability to breakdown VCR and VCR degradation was further increased by adding H 2 O 2 . 2 HOCl is produced in mature myeloid cells, such as neutrophils and has an important role in bacterial neutralization.…”

Section: Discussionmentioning

confidence: 99%

“…1,2,6 MPO-mediated degradation of VCR in the presence of H 2 O 2 has been demonstrated in cellfree systems and leukemia cell lines. 1 This degradation correlated with cellular MPO activity and specific MPO inhibitors blocked VCR degradation. Moreover, MPO anti-sense RNA reduced MPO activity and increased VCR sensitivity.…”

Section: Introductionmentioning

confidence: 96%

“…1,2 Multi-drug resistance (MDR) function is one of the factors known to be associated with the development of VCR resistance. MDR function interferes with intracellular drug accumulation mediated by different effector proteins such as P-glycoprotein (P-gp), MDR-related protein (MRP) and lung resistance protein (LRP).…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2000

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Inherent 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 (H 2 O 2 ). We investigated the relationship between VCR degradation and hypochlorous acid (HOCl) generation from the reaction of H 2 O 2 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 H 2 O 2 and Cl. Leukemia (2000) 14, 47-51.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 96%

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

et al. 2000

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“…Vasculitis (63) and almost all diseases for which no etiology has been identified may potentially be related to abnormal phagocyte functions. Other possible deleterious consequences of phagocyte activities include a potential effect of MPO-mediated oxidation of anticancer drugs such as vincristine (343). Material, such as defensin, released by biomaterialactivated PMNs may contribute to creating an environment hostile to host defenses at the biomaterial surface by cell deactivation.…”

Section: Phagocytes and The Host: "Trick Or Treat"mentioning

confidence: 99%

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

Labro¹

2000

Clinical Microbiology Reviews

151

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“…Importantly, LRP seems to be a prognosticator of poor clinical performance in ovarian cancer and acutc myeloid leukemia. MDR cells may also ovcr-express kinases (Sampson et al, 1993), especially protein kinase C (Posada et al, 1989), as well as other enzymes: e.g., myeloperoxidase (Schlaifer et al, 1993), transglutaminase (Mehta, 1994) and alkaline phosphatase (Uhrik et al, 1994). In some MDR cell lines the cxpression of leukocyte differentiation antigens CD34 (Minderman et al, 1994), CD36 (Sugimoto et al, 1993) and CD56 (Scheper et al, 1991) has been shown to be up-regulated.…”

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confidence: 99%

Evidence for the involvement of ecto-5′-nucleotidase (CD73) in drug resistance

et al. 1996

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Resistance of tumor cells to chemotherapy remains a serious impediment to successful cancer treatment. A multitude of pathways by which neoplastic cclls evade the effects of drugs has been documented (Mihich and Baker, 1994); neverthcless, the search for ncw mechanisms of resistance is far from over.The term "multidrug resistance" (MDR) encompasses all situations arising when exposure to one drug induces not only resistance to that drug but also cross-resistance to other agents to which the cell has not been exposed. Several different proteins have been shown to be associated with this phenomenon; P-glycoprotein 170 (Pgpl70) (Kartner et al., 1983) and MDR-associated protein (MRP) (Cole et al., 1992; Krishnamachary and Center, 1993), members of the ATP-binding cassette transporter family, can protect cells from various lipophilic drugs (e.g., doxorubicin) by mediating their transmembranc export and/or intracellular sequestration. In this way, intracelMar target structures are protected from the effects of drugs. Other wcll-defined mechanisms include modification of topoisomerase 11, increased glutathione transferase levels and increased DNA repair mechanisms (Mihich and Baker, 1994).A variety of other gcnes have been found to bc over- Our group has presentcd evidence that several murine and human MDR tumor cell lines express higher lcvels of the membrane-bound enzymc ecto-5'-nucleotidase (ecto-S'NT; EC 3.1.3.5.) than their respective parental cell lines (Ujhazy et al., 19946). Based on these findings, it was suggested that ecto-5'NT may be involved in MDR (Ujhazy et al., 1994b). Here, further evidence supporting this hypothesis is documented, and a possible function of ecto-5'NT in MDR is suggested. Some of these findings have been presented in preliminary form (Ujhazy et aZ., 1994u, 1995). MATERIAL AND METHODS Cell lines and culture conditwnsCell lines used in this study are described in Table I. The expression of ecto-S'NT is based on previously published data (Ujhizy et al., 1994b) obtained by cytochemical analysis, electron microscopy, immunofluorcscence with specific monoclonal antibodies (MAbs) and AMP sensitivity as a measure of ccto-5'NT enzymatic activity. Standard culture conditions were uscd to maintain and propagate the cell lines throughout the study. RPMI 1640 culture medium (GIBCO, Grand Island, NY) was supplemented with 10% heat-inactivated FCS (Hyclone, Logan, UT), 25 mM HEPES buffer and 0.1 mg/ml of gcntamicin (GIBCO). Northern blot analysisRelative mRNA levels were determined by Northern blotting followed by densitometric evaluation of the autoradiographs. Cells (lo7 to 5 x lo7) were washed with PBS, and total RNA was prepared by lysis in 8 M guanidinium isothiocyanate followed by pelleting through cesium chloride. RNA was quantitated spectrophotometrically (Azrn = 1 at 40 pg/ml). Total RNA from each cell type (50 Fg) were separated by formaldehyde/agarose (1.2%) gel electrophoresis, and the RNA was visualized by UV illumination following staining with ethidium bromide. Using capillary action, ...

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Myeloperoxidase is involved in Vincristine resistance in human myeloblastic leukemia

Cited by 5 publications

References 3 publications

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

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

Interference of Antibacterial Agents with Phagocyte Functions: Immunomodulation or "Immuno-Fairy Tales"?

Evidence for the involvement of ecto-5′-nucleotidase (CD73) in drug resistance

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