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The role of oxidative stress in the cooperation of parthenolide and etoposide in HL-60 cells

Monika A. Papież Oliwia Siodłak Wirginia Krzyściak

Folia Medica Cracoviensia | 2020 | Vol. 60 | No 4 | 5-17 | DOI: 10.24425/fmc.2020.136200

Keywords parthenolide etoposide acute myeloid leukemia GSH oxidative stress flow cytometry

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Abstract

B a c k g r o u n d: The aim of this study was to determine the effect of sesquiterpene lactone parthenolide on the cytotoxic and pro-oxidative effects of etoposide in HL-60 cells.
M e t h o d s: Cytotoxic effects were determined by incubation of HL-60 cells with various concentrations of examined compounds and combinations thereof, which were then stained with propidium iodide and analyzed using a flow cytometer. To determine the role of oxidative stress in the action of the compounds, co-incubation with N-acetyl-l-cysteine (NAC) and parthenolide and/or etoposide was used and the level of reduced glutathione (GSH) was detected.
R e s u l t s: Parthenolide significantly enhanced the cytotoxic and pro-apoptotic effects of etoposide. However, in most cases of the combinations of parthenolide and etoposide, their effect was antagonistic, as confirmed by an analysis using the CalcuSyn program. The examined compounds significantly reduced the level of GSH in HL-60 cells. Combination of etoposide at a concentration of 1.2 μM and parthenolide also significantly reduced GSH level. However, in the case of a combination of etoposide at a concentration of 2.5 μM with parthenolide, a significant increase in the level of GSH was obtained compared to compounds acting alone. This last observation seems to confirm the antagonism between the compounds tested.
C o n c l u s i o n s: Parthenolide did not limit the cytotoxic effect of etoposide in HL-60 cells even in the case of antagonistic interaction. If parthenolide does increase GSH levels in combination with etoposide in the normal hematopoietic cells, it could protect them against the pro-oxidative effects of this anti-cancer drug.

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Authors and Affiliations

Monika A. Papież

Oliwia Siodłak

Wirginia Krzyściak

Department of Cytobiology, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland
Department of Medical Diagnostic, Faculty of Pharmacy, Jagiellonian University Medical College, Kraków, Poland

Outcomes of Jehovah’s Witnesses with hematological malignancies treated without transfusions — single center experience

Joanna Ewa Drozd-Sokołowska Anna Waszczuk-Gajda Jadwiga Dwilewicz-Trojaczek Alicja Walesiak Monika Krzyżanowska Monika Paluszewska Jolanta Wieczorek Wiesław Wiktor-Jędrzejczak

Folia Medica Cracoviensia | 2020 | Vol. 60 | No 4 | 53-64 | DOI: 10.24425/fmc.2020.136204

Keywords Jehovah’s Witnesses leukemia lymphoma blood transfusion platelet transfusion

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Abstract

Malignancies of the hematopoietic system frequently are associated with severe cytopenias requiring transfusions of blood components. Refusal of blood components by Jehovah’s Witnesses (JW) produces challenges to treatment. In this report we describe the outcome of hematological malignancies of JW patients treated without transfusions. Altogether, eight JW, diagnosed 1994–2015, 6 (75%) females, the median age at diagnosis 40 years (range, 20–78), were included into the analysis. The diagnoses were: acute lymphoblastic leukemia (2, 25%), acute myeloid leukemia (2, 25%), non-Hodgkin’s lymphomas (4, 50%). One patient died without treatment while the remaining 7 patients received treatment, including imatinib in 1 patient with BCR-ABL1+ acute lymphoblastic leukemia. Five (62.5%) patients received erythropoiesis stimulating agents. Median hemoglobin concentration at diagnosis was 8.7 g/dL (range, 6.3–13.1), and it decreased to 3.2 g/dL (range, 2.6–9.3) during first-line treatment. Median platelet count at diagnosis was 52 × 109/L (range, 15–392). All patients became thrombocytopenic upon treatment reaching median platelet count 8 × 109/L (range, 2–85). Five patients developed respiratory failure. Anemia contributed substantially to the death of 3 out of 6 patients (50%). One patient (17%) developed central nervous system bleeding in the course of thrombocytopenia. Objective response rate was 43%, with 29% complete remissions after first-line treatment. Despite the median overall survival of 15.3 months (95% CI, 0.2–52.2), all but one acute leukemia patients succumbed shortly after the diagnosis. To conclude, the outcome of JW treated because of hematological malignancies without blood transfusions is very dismal, nevertheless, selected patients can obtain complete remissions. Anemia contributes significantly to the death of JW.

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Authors and Affiliations

Joanna Ewa Drozd-Sokołowska

Anna Waszczuk-Gajda

Jadwiga Dwilewicz-Trojaczek

Alicja Walesiak

Monika Krzyżanowska

Monika Paluszewska

Jolanta Wieczorek

Wiesław Wiktor-Jędrzejczak

Department of Hematology, Transplantation and Internal Medicine, Medical University of Warsaw, Poland

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The role of oxidative stress in the cooperation of parthenolide and etoposide in HL-60 cells

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Authors and Affiliations

Outcomes of Jehovah’s Witnesses with hematological malignancies treated without transfusions — single center experience

Abstract

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Authors and Affiliations