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Journals / Mustafa Kemal Üniversitesi Tıp Dergisi / 2022 / Cilt: 13 - Sayı: 46

The effect of proteasome inhibitor Carfilzomib on pyroptosis cell death pathway in multiple myeloma cells

Proteozom inhibitörü Carfilzomib’in multipl miyelom hücrelerinde piroptozis hücre ölüm yolağı üzerine olan etkisi

Dilara AKÇORA YILDIZ
Yakuphan BAYKAN
Fadime AŞIK
Pages
132–137
Publication Date
2022-10-19
DOI
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Results: CFZ treatment led to a significant increase in GSDMD and GSDME mRNA levels in NCI H929 and RPMI 8226 cells, while a remarkable increase was detected only in GSDME mRNA levels in U266 cells (p

📌 3 Key Takeaways

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Objective & Hypothesis:Objective: Multiple myeloma (MM), characterized by excessive accumulation of monoclonal antibody-secreting abnormal plasma cells in the bone marrow, is a B-cell malignancy.
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Key Findings & Data:Methods: Human NCI H929, RPMI 8226, and U266 MM cell lines were treated with IC50 doses of CFZ for 48 hours.
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Conclusion & Impact:Results: CFZ treatment led to a significant increase in GSDMD and GSDME mRNA levels in NCI H929 and RPMI 8226 cells, while a remarkable increase was detected only in GSDME mRNA levels in U266 cells (p
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Multipl Miyelom · Proteazom İnhibitörü · Carfilzomib

Abstract

Objective: Multiple myeloma (MM), characterized by excessive accumulation of monoclonal antibody-secreting abnormal plasma cells in the bone marrow, is a B-cell malignancy. In clinical practice, the second-generation proteasome inhibitor Carfilzomib (CFZ) is used in the treatment regimens of relapsed or treatment-resistant patients. However, the mechanisms of CFZ-induced cell death in MM cells have not been fully elucidated. The aim of this study is to investigate the effect of CFZ on pyroptosis, which is one of the regulated non-apoptotic cell death pathways in MM cells. Methods: Human NCI H929, RPMI 8226, and U266 MM cell lines were treated with IC50 doses of CFZ for 48 hours. In treated cells, the differences in mRNA levels of GSDMD and GSDME, which are important substrates of pyroptosis, and in mRNA levels of Bax as well as in mRNA levels of Bcl-2 were determined by quantitative real-time PCR (qPCR) method. Results: CFZ treatment led to a significant increase in GSDMD and GSDME mRNA levels in NCI H929 and RPMI 8226 cells, while a remarkable increase was detected only in GSDME mRNA levels in U266 cells (p

Özet

Amaç: Multipl miyelom (MM), monoklonal antikor salgılayan anormal plazma hücrelerinin kemik iliğinde aşırı birikimi ile karakterize bir B hücre malignitesidir. Klinik uygulamalarda ikinci nesil proteozom inhibitörü carfilzomib (CFZ), relaps veya tedaviye dirençli hastaların tedavi rejimlerinde kullanılmaktadır. Ancak, MM hücrelerinde CFZ’in tetiklediği hücre ölümü mekanizmaları tam olarak aydınlatılamamıştır. Bu çalışmanın amacı, MM hücrelerinde CFZ’in apoptotik olmayan düzenli hücre ölüm yolaklarından biri olan piroptozis üzerine olan etkisinin araştırılmasıdır. Yöntem: İnsan RPMI 8226, U266 ve NCI H929 MM hücre hatları, CFZ’in IC50 dozları ile 48 saat süre boyunca muamele edildi. Muamele edilen hücrelerde piroptozisin önemli substratları olan GSDMD ve GSDME ile Bax ve Bcl-2 genlerinin mRNA düzeylerindeki farklılıklar kantitatif eş zamanlı PCR (qPCR) yöntemiyle belirlendi. Bulgular: NCI H929 ve RPMI 8226 hücrelerinde CFZ uygulamasının hem GSDMD hem de GSDME mRNA düzeylerinde anlamlı artışa neden olduğu belirlenirken, U266 hücrelerinde ise sadece GSDME mRNA seviyesinde anlamlı bir artış tespit edildi (p

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Cite This Article

YILDIZ, D. A., BAYKAN, Y., AŞIK, F. (2022). The effect of proteasome inhibitor Carfilzomib on pyroptosis cell death pathway in multiple myeloma cells. Mustafa Kemal Üniversitesi Tıp Dergisi, Cilt: 13 - Sayı: 46, 132–137. https://ajindex.com/articles/583258

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References (10)

  1. Corre J, Munshi NC, Avet-Loiseau H. Risk factors in multiple myeloma: is it time for a revision? Blood. 2021;137(1): 16-19. https://doi.org/10.1182/blood.2019004309. Groen K, van de Donk NWCJ, Stege C, Zweegman S, Nijhof IS. Carfilzomib for relapsed and refractory multiple myeloma. Cancer Manag Res. 2019;11: 2663-2675. https://doi.org/10.2147/CMAR.S150653.
  2. Galluzzi L, Vitale I, Aaronson SA, Abrams JM, Adam D, Agostinis P, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ. 2018;25(3): 486-541. https://doi.org/10.1038/s41418-017-0012-4.
  3. Robinson N, Ganesan R, Hegeds C, Kovács K, Kufer TA, Virág L. Programmed necrotic cell death of macrophages: Focus on pyroptosis, necroptosis, and parthanatos. Redox Biol. 2019;26: 101239. https://doi.org/10.1016/j.redox.2019.101239.
  4. Touzeau C, Maciag P, Amiot M, Moreau P. Targeting Bcl-2 for the treatment of multiple myeloma. Leukemia. 2018;32(9): 1899-1907. https://doi.org/10.1038/s41375-018-0223-9.
  5. Shi C-S, Kehrl JH. Bcl-2 regulates pyroptosis and necroptosis by targeting BH3-like domains in GSDMD and MLKL. Cell Death Discov. 2019; 9;5: 151. https://doi.org/10.1038/s41420-019-0230-2.
  6. Maral S, Albayrak M, Pala Ç. Current Treatment Approaches to Multiple Myeloma with New Agents. J Clin Exp Investig. 2018;9(2): 103-112 https://doi.org/10.5799/jcei.433823 Ri M. Endoplasmic-reticulum stress pathway-associated mechanisms of action of proteasome inhibitors in multiple myeloma. Int J Hematol. 2016;104(3):.273-80. https://doi.org/10.1007/s12185-016-2016-0.
  7. Fadeel B, Orrenius S. Apoptosis: a basic biological phenomenon with wide-ranging implications in human disease. J Intern Med. 2005;258(6): 479-517. https://doi.org/10.1111/j.1365-2796.2005.01570.x.
  8. Kuhn DJ, Chen Q, Voorhees PM, Strader JS, Shenk KD, Sun CM, et al. Potent activity of carfilzomib, a novel, irreversible inhibitor of the ubiquitin-proteasome pathway, against preclinical models of multiple myeloma. Blood. 2007;110(9): 3281-90. https://doi.org/10.1182/blood-2007-01-065888.
  9. Han B, Yao W, Oh Y-T, Tong J-S, Li S, Deng J, et al. The novel proteasome inhibitor carfilzomib activates and enhances extrinsic apoptosis involving stabilization of death receptor 5. Oncotarget. 2015;6(19): 17532-42. https://doi.org/10.18632/oncotarget.3947.
  10. Moriwaki K, Chan FK-M. Regulation of RIPK3- and RHIM-dependent Necroptosis by the Proteasome. J Biol Chem. 2016;291(11): 5948-5959. https://doi.org/10.1074/jbc.M115.700