The effect of Thymoquinone on Peripheral Blood Mononuclear Cells (PBMCs) viability of patients with B-Chronic Lymphocytic Leukemia

authors:

avatar Maral Hemati ORCID , avatar Maryam Abdollahi , avatar Mehrnoosh Pashaei ORCID , avatar Farahnaz Ghahremanfard ORCID , avatar Parviz Kokhaei ORCID , *

Koomesh: Vol.25, issue 2; 145-151
published online: September 01, 2023
article type: Research Article
received: August 03, 2022
accepted: March 01, 2023

how to cite: Hemati M, Abdollahi M, Pashaei M, Ghahremanfard F, Kokhaei P. The effect of Thymoquinone on Peripheral Blood Mononuclear Cells (PBMCs) viability of patients with B-Chronic Lymphocytic Leukemia. koomesh. 2023;25(2):e152812. 

Abstract

Introduction: Chronic lymphocytic leukemia (CLL) as a lymphoproliferative disorder that is characterized by the expansion of monoclonal, mature CD5+CD23+ B cells in the peripheral blood, secondary lymphoid tissues, and bone marrow is facing with advent of new therapies targeting crucial biological pathways. Thymoquinone (TQ) is the major bioactive constituent in black seed oil (Nigella sativa) and has been found to exert anti-tumor impacts mainly through the induction of apoptosis. This study aimed to evaluate the in vitro anti-leukemia effects of TQ on peripheral blood mononuclear cells (PBMCs) of CLL patients. Materials and Methods: Peripheral blood mononuclear cells (PBMCs) of 6 patients and 6 healthy donors were treated with 15 μg/ml of TQ for 24 h. The cytotoxic effect of TQ was assessed using the MTT assay. Flow cytometry was used to analyze the apoptosis of PBMCs. Results: Treatment with TQ increased the cytotoxicity of PBMCs of CLL patients more significantly than in Untreated cells (P=0.021). Flow cytometry results indicated that TQ exhibited a significant apoptotic impact on PBMCs of CLL patients compared to the healthy subjects (P=0.001). TQ also induced marked apoptosis in CLL cells compared to the Untreated cells (P=0.006). Conclusion: Our findings reveal that TQ possesses promising therapeutic potential as an anti-tumor agent for treating CLL mainly through the induction of cell apoptosis and cytotoxicity.

References

  • 1.

    Ten Hacken E, Burger JA. Microenvironment interactions and B-cell receptor signaling in chronic lymphocytic leukemia: Implications for disease pathogenesis and treatment. Biochim Biophys Acta 2016; 1863: 401-413.

  • 2.

    Kokhaei P. B-cell chronic lymphocyte leukemia (B-CLL). Koomesh 1386; 9: 1-12. (Persian).

  • 3.

    Koohi F, Salehiniya H, Shamlou R, Eslami S, Ghojogh ZM, Kor Y, Rafiemanesh H. Leukemia in Iran: Epidemiology and morphology trends. Asian Pacific J Cancer Prev 2015; 16: 7759-7763.

  • 4.

    Pulte D, Redaniel MT, Bird J, Jeffreys M. Survival for patients with chronic leukemias in the US and Britain: agerelated disparities and changes in the early 21st century. Eur J Haematol 2015; 94: 540-545.

  • 5.

    Visone R, Veronese A, Rassenti LZ, Balatti V, Pearl DK, Acunzo M, et al. miR-181b is a biomarker of disease progression in chronic lymphocytic leukemia. Blood 2011; 118: 3072-3079.

  • 6.

    Sadeghnejad A, Hemati M, Pashaei M, Rasouli Nejad Z, Ghahremanfard F, Kokhaei P. Effect of IL-27 on activity of bone marrow NK cells of patient with B-chronic lymphocytic leukemia in vitro. Koomesh 1399; 23: 131-138. (Persian)##https://doi.org/10.29252/koomesh.23.1.131.

  • 7.

    Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N E J Med 2014; 370: 1101-1110.

  • 8.

    Hallek M, Fischer K, Fingerle-Rowson G, Fink A, Busch R, Mayer J, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukaemia: a randomised, open-label, phase 3 trial. The Lancet 2010; 376: 1164-1174.

  • 9.

    Taylor WF, Jabbarzadeh E. The use of natural products to target cancer stem cells. Am J Cancer Res 2017; 7: 1588-1605.

  • 10.

    Parikh SA. Chronic lymphocytic leukemia treatment algorithm 2018. Blood Cancer J 2018; 8: 93.

  • 11.

    Sauter ER. Cancer prevention and treatment using combination therapy with natural compounds. Exp Rev Clin Pharmacol 2020; 13: 265-285.

  • 12.

    Ratovitski EA. Anticancer natural compounds as epigenetic modulators of gene expression. Curr Genom 2017; 18: 175-205.

  • 13.

    Fatfat Z, Fatfat M, Gali-Muhtasib H. Therapeutic potential of thymoquinone in combination therapy against cancer and cancer stem cells. World J Clin Oncol 2021; 12: 522-543.

  • 14.

    Ahmad A, Mishra RK, Vyawahare A, Kumar A, Rehman MU, Qamar W, et al. Thymoquinone (2-Isopropyl-5-methyl-1, 4-benzoquinone) as a chemopreventive/anticancer agent: Chemistry and biological effects. Saudi Pharmace J 2019; 27: 1113-1126.

  • 15.

    Amizadeh S, Rashtchizadeh N, Khabbazi A, Ghorbanihaghjo A, Ebrahimi AA, Vatankhah AM, et al. Effect of Nigella sativa oil extracts on inflammatory and oxidative stress markers in Behcet's disease: A randomized, double-blind, placebo-controlled clinical trial. Avicenna J Phytomed 2020; 10: 181.

  • 16.

    Nawarathne NW, Wijesekera K, Wijayaratne WM, Napagoda M. Development of novel topical cosmeceutical formulations from Nigella sativa L. with antimicrobial activity against acne-causing microorganisms. Scientific World J 2019; 2019.

  • 17.

    Hamada F, Abdel-Aziz H, Badr F, Moustafa A, Rashad A. The mutagenic effect of praziquantel in S. mansoni-infected mice. Arab J Lab 1992; 18: 301-311.

  • 18.

    Salim EI, Fukushima S. Chemopreventive potential of volatile oil from black cumin (Nigella sativa L.) seeds against rat colon carcinogenesis. Nutr Cancer 2003; 45: 195-202.

  • 19.

    Woo CC, Loo SY, Gee V, Yap CW, Sethi G, Kumar AP, Tan KH. Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR- pathway. Biochem Pharmacol 2011; 82: 464-475.

  • 20.

    Awad E. In vitro decreases of the fibrinolytic potential of cultured human fibrosarcoma cell line, HT1080, by Nigella sativa oil. Phytomedicine 2005; 12: 100-107.

  • 21.

    Bargi R, Hosseini M, Asgharzadeh F, Khazaei M, Shafei MN, Beheshti F. Protection against blood-brain barrier permeability as a possible mechanism for protective effects of thymoquinone against sickness behaviors induced by lipopolysaccharide in rats. Jundishapur J Nat Pharmac Prod 2021; 16. (Persian)##https://doi.org/10.5812/jjnpp.67765.

  • 22.

    Khan MA, Tania M, Wei C, Mei Z, Fu S, Cheng J, et al. Thymoquinone inhibits cancer metastasis by downregulating TWIST1 expression to reduce epithelial to mesenchymal transition. Oncotarget 2015; 6: 19580.

  • 23.

    Khan MA, Tania M, Fu S, Fu J. Thymoquinone, as an anticancer molecule: from basic research to clinical investigation. Oncotarget 2017; 8: 51907.

  • 24.

    Peng L, Liu A, Shen Y, Xu HZ, Yang SZ, Ying XZ, et al. Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-B pathway. Oncol Rep 2013; 29: 571-578.

  • 25.

    Hallek M, Cheson BD, Catovsky D, Caligaris-Cappio F, Dighiero G, Dhner H, et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood 2008; 111: 5446-5456.

  • 26.

    Jain P, Keating M, Wierda W, Estrov Z, Ferrajoli A, Jain N, et al. Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib. Blood 2015; 125: 2062-2067.

  • 27.

    Edris AE. Anti-cancer properties of Nigella spp. essential oils and their major constituents, thymoquinone and beta-elemene. Curr Clin Pharmacol 2009; 4: 43-46.

  • 28.

    Cragg GM, Grothaus PG, Newman DJ. Impact of natural products on developing new anti-cancer agents. Chem Rev 2009; 109: 3012-3043.

  • 29.

    Jain P, Keating M, Wierda W, Estrov Z, Ferrajoli A, Jain N, et al. Outcomes of patients with chronic lymphocytic leukemia after discontinuing ibrutinib. Blood 2015; 125: 2062-2067.

  • 30.

    Yi T, Cho SG, Yi Z, Pang X, Rodriguez M, Wang Y, et al. Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Mol Cancer Ther 2008; 7: 1789-96.

  • 31.

    Al-Johar D, Shinwari N, Arif J, Al-Sanea N, Jabbar AA, El-Sayed R, et al. Role of Nigella sativa and a number of its antioxidant constituents towards azoxymethane-induced genotoxic effects and colon cancer in rats. Phytother Res 2008; 22: 1311-1323.

  • 32.

    Salim LZ, Othman R, Abdulla MA, Al-Jashamy K, Ali HM, Hassandarvish Pet al. Thymoquinone inhibits murine leukemia WEHI-3 cells in vivo and in vitro. PloS One 2014; 9: e115340.

  • 33.

    Goldsworthy TL, Conolly RB, Fransson-Steen R. Apoptosis and cancer risk assessment. Mutat Res 1996; 365: 71-90.

  • 34.

    Nagata S. Apoptotic DNA fragmentation. Exp Cell Res 2000; 256: 12-18.

  • 35.

    Musalli MG, Hassan MA, Sheikh RA, Kalantan AA, Halwani MA, Zeyadi M, et al. Thymoquinone induces cell proliferation inhibition and apoptosis in acute myeloid leukemia cells: Role of apoptosis-related WT1 and BCL2 genes. Eur J Cell Sci 2019; 1: 2-9.##https://doi.org/10.34154/2019-EJCS-0101-02-09/euraass.

  • 36.

    Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Thymoquinone-induced antitumor and apoptosis in human lung adenocarcinoma cells. J Cell Physiol 2019; 234: 10421-10431.