Osteopontin siRNA does not confer resistance to toxic effects of parthenolide in Jurkat cells
DOI:
https://doi.org/10.32471/exp-oncology.2312-8852.vol-42-no-3.15180Keywords:
Jurkat cells, osteopontin, parthenolideAbstract
Summary. Background: Osteopontin (OPN) plays a critical role in cell proliferation and drug resistance in cancer treatment and hematological malignancies. In T cell acute lymphoblastic leukemia, most initial therapies can induce remission while some patients then relapse and do not respond well to chemotherapy. The sesquiterpene lactone parthenolide (PTL) can induce apoptosis in a variety of cancer cell lines via inhibition of pro-inflammatory transcription factor nuclear factor kappa B and has anti-tumor activity in acute lymphoblastic leukemia treatment. Aim: To study the role of OPN in conferring in vitro resistance to PTL in Jurkat cells. Methods: Jurkat cells were cultured with 8–20 μm PTL for 48 h. Transfection with OPN siRNA was provided. Apoptosis assays were performed with Annexin V-Alexa Fluor-488/PI. Quantitative real-time polymerase chain reaction was used to measure OPN gene expression using the 2-2-ΔΔCt method. Results: PTL has cytotoxic and apoptotic effect on Jurkat cells with IC50 values of 16.1 μm, and growth inhibition effect of PTL does not differ significantly in combination with OPN-siRNA. OPN gene expression is not affected by PTL. Conclusions: Parthenolide induces apoptosis in Jurkat cells, but inhibition of osteopontin gene expression with siRNA does not reduce apoptotic effect of parthenolide.
References
Mazzali M, Kipari T, Ophascharoensuk V, et al. Osteopontin — a molecule for all seasons. QJM 2002; 95: 3–13.
Lee GS, Salazar HF, Joseph G, et al. Osteopontin isoforms differentially promote arteriogenesis in response to ischemia via macrophage accumulation and survival. Lab Invest 2019; 99: 331–45.
Boyerinas B, Zafrir M, Yesilkanal AE, et al. Adhesion to osteopontin in the bone marrow niche regulates lymphoblastic leukemia cell dormancy. Blood 2013; 121: 4821–31.
Shevde LA, Samant RS. Role of osteopontin in the pathophysiology of cancer. Matrix Biol 2014; 37: 131–41.
Nilsson SK, Johnston HM, Whitty GA, et al. Osteopontin, a key component of the hematopoietic stem cell niche and regulator of primitive hematopoietic progenitor cells. Blood 2005; 106: 1232–9.
Mandarapu R, Prakhya BM. Exposure to cypermethrin and mancozeb alters the expression profile of THBS1, SPP1, FEZ1 and GPNMB in human peripheral blood mononuclear cells. J Immunotoxicol 2016; 13: 463–73.
El-Tanani MK, Campbell FC, Kurisetty V, et al. The regulation and role of osteopontin in malignant transformation and cancer. Cytokine Growth Factor Rev 2006; 17: 463–74.
Sharif SA, Du X, Myles T, et al. Thrombin‐activatable carboxypeptidase B cleavage of osteopontin regulates neutrophil survival and synoviocyte binding in rheumatoid arthritis. Arthritis Rheum 2009; 60: 2902–12.
Myles T, Nishimura T, Yun TH, et al. Thrombin activatable fibrinolysis inhibitor, a potential regulator of vascular inflammation. J Biol Chem 2003; 278: 51059–67.
Steele A, Jones D, Ganeshaguru K, et al. The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic lymphocytic leukemia cells in vitro. Leukemia 2006; 20: 1073–9.
Weber G. Osteopontin-based cancer therapies. Patent USA 2004; US20060252684A1. Retrieved from: https://patents.google.com/patent/US20060252684
Li‐Weber M, Giaisi M, Treiber MK, et al. The anti‐inflammatory sesquiterpene lactone parthenolide suppresses IL‐4 gene expression in peripheral blood T cells. Eur J Immunol 2002; 32: 3587–97.
Nakshatri H, Rice SE, Bhat-Nakshatri P. Antitumor agent parthenolide reverses resistance of breast cancer cells to tumor necrosis factor-related apoptosis-inducing ligand through sustained activation of c-Jun N-terminal kinase. Oncogene 2004; 23: 7330–44.
Anderson KN, Bejcek BE. Parthenolide induces apoptosis in glioblastomas without affecting NF-κB. J Pharmacol Sci 2008; 106: 318–20.
Li-Weber M, Giaisi M, Baumann S, et al. The anti-inflammatory sesquiterpene lactone parthenolide suppresses CD95-mediated activation-induced-cell-death in T-cells. Cell Death Differ 2002; 9: 1256–65.
Li-Weber M, Palfi K, Giaisi M, et al. Dual role of the anti-inflammatory sesquiterpene lactone: regulation of life and death by parthenolide. Cell Death Differ 2005; 12: 408–9.
Pozarowski P, Halicka DH, Darzynkiewicz Z. Cell cycle effects and caspase-dependent and independent death of HL-60 and Jurkat cells treated with inhibitor of NF-6B parthenolide. Cell Cycle 2003; 2: 374–80.
Cario G, Stanulla M, Fine BM, et al. Distinct gene expression profiles determine molecular treatment response in childhood acute lymphoblastic leukemia. Blood 2005; 105: 821–6.
Zahedpanah M, Shaiegan M, Ghaffari SH, et al. Parthenolide induces apoptosis in committed progenitor AML cell line U937 via reduction in osteopontin. Rep Biochem Mol Biol 2016; 4: 82–8.
Mohammadi S, Zahedpanah M, Ghaffari SH, et al. Osteopontin plays a unique role in resistance of CD34+/CD123+ human leukemia cell lines KG1a to parthenolide. Life Sci 2017; 189: 89–95.
Mirzaei A, Mohammadi S, Ghaffari SH, et al. Osteopontin b and c splice isoforms in leukemias and solid tumors: angiogenesis alongside chemoresistance. Asian Pac J Cancer Prev 2018; 19: 615–23.
Panah MZ, Nikbakht M, Sajjadi SM, et al. Anti-apoptotic effects of osteopontin via the up-regulation of AKT/mTOR/β-catenin loop in acute myeloid leukemia cells. Int J Hematol Oncol Stem Cell Res 2017; 11: 148–57.
Huang X, Chen S, Shen Q, et al. Analysis of the expression pattern of the BCL11B gene and its relatives in patients with T-cell acute lymphoblastic leukemia. J Hematol Oncol 2010; 3: 44.
Holleman A, Cheok MH, den Boer ML, et al. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment. N Engl J Med 2004; 351: 533–42.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
