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Indian Journal of Hematology and Blood Transfusion

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08.12.2016 | Original Article

Antiproliferative and Apoptosis-Inducing Activities of Thymoquinone in Lymphoblastic Leukemia Cell Line

verfasst von: Amin Soltani, Batoul Pourgheysari, Hedayatollah Shirzad, Zahra Sourani

Erschienen in: Indian Journal of Hematology and Blood Transfusion | Ausgabe 4/2017

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Abstract

Acute lymphoblastic leukemia is one of the malignant proliferations of lymphoid cells in the early stages of differentiation and accounts for about 80% of all cases of childhood leukemia. Side effects of available treatment are still main concern. Thymoquinone (TQ), a natural compound isolated from Nigella sativa, induces growth inhibition and apoptosis in several cancer cell lines. The aim of the present study was to investigate the effect of TQ alone and in combination with doxorubicine on the proliferation inhibition and apoptosis induction of TQ in a lymphoblastic leukemia cell line. Jurkat cell line was cultured in standard condition and with concentrations of TQ (0–30 μm) and doxorubicine for 24, 48 and 72 h. Cell viability was measured by MTS assay. Apoptosis induction by TQ was assessed by annexin V-FITC/PI and flow cytometry analysis. TQ and DOX decreased cell viability with a time and dose dependent manner. The IC50 values were 19.461 ± 1.141, 17.342 ± 1.949 and 14.123 ± 1.874 μM in 24, 48 and 72 h, respectively for TQ. IC50 values for DOX were. 075 ± .0124, .028 ± .007 and.007 ± .001 μM in 24, 48 and 72 h, respectively. The level of cell apoptosis in all used concentrations of TQ (4, 8, 12, 16 and 20 μm) was higher than control group (10.2, 14.1, 36.6, 87.5 and 93.3% respectively after 24 h; 10.7, 13.9, 64.6, 92.2 and 93.1 respectively after 48 h; 2.83, 5.83, 41.4, 71.6 and 86.6% respectively after 72 h) and reached to a significant level at 12, 16 and 20 μm concentration for 24 and 48 h and 16 and 20 μm for 72 h incubation. Combination of doxorubicine and TQ lead to a synergistic cytotoxicity as compared to any of them alone. The study indicated that TQ is effective on proliferation inhibition and is a strong apoptotic inducer in Jurkat lymphoblastic cell line and has synergistic effect in combination with DOX. This combination strategy can be an alternative way for more powerful anticancer effects. Therefore, the study of the mechanism of apoptosis induction of TQ can be a step forward to in target therapy which might be considered in the future studies.

Peregud-Pogorzelski J (2014) How have advances in our understanding of the molecular genetics of paediatric leukaemia led to improved targeted therapies for these diseases? Clin Exp Med 23(3):469–474

Pyatt D, Hays S (2010) A review of the potential association between childhood leukemia and benzene. Chem Biol Interact 184(1):151–164CrossRefPubMed

Narayanan S, Shami PJ (2012) Treatment of acute lymphoblastic leukemia in adults. Crit Rev Oncol Hematol 81(1):94–102CrossRefPubMed

Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C et al (2006) Cancer statistics, 2006. CA Cancer J 56(2):106–130CrossRef

Roti G, Stegmaier K (2014) New approaches to target T-ALL. Front Oncol 4:201–211CrossRef

Ebinger M, Witte K-E, Ahlers J, Schäfer I, André M, Kerst G et al (2010) High frequency of immature cells at diagnosis predicts high minimal residual disease level in childhood acute lymphoblastic leukemia. Leuk Res 34(9):1139–1142CrossRefPubMed

Vuorela P, Leinonen M, Saikku P, Tammela P, Rauha J-P, Wennberg T et al (2004) Natural products in the process of finding new drug candidates. Curr Med Chem 11(11):1375–1389CrossRefPubMed

Woo CC, Kumar AP, Sethi G, Tan KHB (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83(4):443–451CrossRefPubMed

Abel-Salam BK (2012) Immunomodulatory effects of black seeds and garlic on alloxan-induced diabetes in albino rat. Allergol Immunopathol 40(6):336–340CrossRef

10.

Gali-Muhtasib H, Roessner A, Schneider-Stock R (2006) Thymoquinone: a promising anti-cancer drug from natural sources. Int J Biochem Cell Biol 38(8):1249–1253CrossRefPubMed

11.

Shoieb AM, Elgayyar M, Dudrick PS, Bell JL, Tithof PK (2003) In vitro inhibition of growth and induction of apoptosis in cancer cell lines by thymoquinone. Int J Oncol 22(1):107–113PubMed

12.

Ivankovic S, Stojkovic R, Jukic M, Milos M, Milos M, Jurin M (2006) The antitumor activity of thymoquinone and thymohydroquinone in vitro and in vivo. Exp Oncol 28(3):220–224PubMed

13.

Womack K, Anderson M, Tucci M, Hamadain E, Benghuzzi H (2005) Evaluation of bioflavonoids as potential chemotherapeutic agents. Biomed Sci Instrum 42:464–469

14.

Banerjee S, Kaseb AO, Wang Z, Kong D, Mohammad M, Padhye S et al (2009) Antitumor activity of gemcitabine and oxaliplatin is augmented by thymoquinone in pancreatic cancer. Cancer Res 69(13):5575–5583CrossRefPubMed

15.

Kaseb AO, Chinnakannu K, Chen D, Sivanandam A, Tejwani S, Menon M et al (2007) Androgen receptor-and E2F-1-targeted thymoquinone therapy for hormone-refractory prostate cancer. Cancer Res 67(16):7782–7788CrossRefPubMed

16.

Yi T, Cho S-G, Yi Z, Pang X, Rodriguez M, Wang Y et al (2008) Thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing AKT and extracellular signal-regulated kinase signaling pathways. Mol Cancer Ther 7(7):1789–1796CrossRefPubMedPubMedCentral

17.

Sethi G, Ahn KS, Aggarwal BB (2008) Targeting nuclear factor-κB activation pathway by thymoquinone: role in suppression of antiapoptotic gene products and enhancement of apoptosis. Mol Cancer Biol 6(6):1059–1070

18.

Worthen DR, Ghosheh OA, Crooks P (1997) The in vitro anti-tumor activity of some crude and purified components of blackseed, Nigella sativa L. Anticancer Res 18(3A):1527–1532

19.

Gali-Muhtasib H, Kuester D, Mawrin C, Bajbouj K, Diestel A, Ocker M et al (2008) Thymoquinone triggers inactivation of the stress response pathway sensor CHEK1 and contributes to apoptosis in colorectal cancer cells. Cancer Res 68(14):5609–5618CrossRefPubMed

20.

Banerjee S, Padhye S, Azmi A, Wang Z, Philip PA, Kucuk O et al (2010) Review on molecular and therapeutic potential of thymoquinone in cancer. Nutr Cancer 62(7):938–946CrossRefPubMedPubMedCentral

21.

Goldsworthy TL, Conolly RB, Fransson-Steen R (1996) Apoptosis and cancer risk assessment. Mutat Res Rev Genet 365(1):71–90CrossRef

22.

Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10(2):86–103CrossRefPubMedPubMedCentral

23.

Khalil AA, Kabapy NF, Deraz SF, Smith C (2011) Heat shock proteins in oncology: diagnostic biomarkers or therapeutic targets? Biochim Biophys Acta 1816(2):89–104PubMed

24.

Lee W-J, Hsiao M, Chang J-L, Yang S-F, Tseng T-H, Cheng C-W et al (2015) Quercetin induces mitochondrial-derived apoptosis via reactive oxygen species-mediated ERK activation in HL-60 leukemia cells and xenograft. Arch Toxicol 89(7):1103–1117CrossRefPubMed

25.

Rahimnejad T, Beshkar P, Shirzad H, Rafieian- Kopaei M, Safdari V, Asgarian N et al (2014) Effect of pterostilbene in cellular proliferation inhibition and induction of apoptosis in lymphoblastic leukemia cell line. J Babol Univ Med Sci 16(12):32–38

26.

Chou T-C, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzyme Regul 22:27–55CrossRefPubMed

27.

Bauer J, Wekerle H, Lassmann H (1995) Apoptosis in brain-specific autoimmune disease. Curr Opin Immunol 7(6):839–843CrossRefPubMed

28.

Dergarabetian E, Ghattass K, El-Sitt S, Al-Mismar R, El-Baba C, Itani W et al (2012) Thymoquinone induces apoptosis in malignant T-cells via generation of ROS. Front Biosci 5:706–719

29.

Zihlif MA, Mahmoud IS, Ghanim MT, Zreikat MS, Alrabadi N, Imraish A et al (2013) Thymoquinone efficiently inhibits the survival of EBV-infected B cells and alters EBV gene expression. Integr Cancer Ther 12(3):257–263CrossRefPubMed

30.

Effenberger-Neidnicht K, Schobert R (2011) Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin. Cancer Chemother Pharmacol 67(4):867–874CrossRefPubMed

31.

El-Mahdy MA, Zhu Q, Wang QE, Wani G, Wani AA (2005) Thymoquinone induces apoptosis through activation of caspase-8 and mitochondrial events in p53-null myeloblastic leukemia HL-60 cells. Int J Cancer 117(3):409–417CrossRefPubMed

32.

Richards L, Jones P, Hughes J, Benghuzzi H, Tucci M (2005) The physiological effect of conventional treatment with epigallocatechin-3-gallate, thymoquinone, and tannic acid on the LNCaP cell line. Biomed Sci Instrum 42:357–362

33.

Li Q, Yu D, Liu G, Ke N, McKelvy J, Wong-Staal F (2008) Selective anticancer strategies via intervention of the death pathways relevant to cell transformation. Cell Death Differ 15(8):1197–1210CrossRefPubMed

34.

Woo CC, Loo SY, Gee V, Yap CW, Sethi G, Kumar AP et al (2011) Anticancer activity of thymoquinone in breast cancer cells: possible involvement of PPAR-γ pathway. Biochem Pharmacol 82(5):464–475CrossRefPubMed

35.

Abdelfadil E, Cheng Y-H, Bau D-T, Ting W-J, Chen L-M, Hsu H-H et al (2013) Thymoquinone induces apoptosis in oral cancer cells through p38β inhibition. Am J Chin Med 41(03):683–696CrossRefPubMed

36.

Ng WK, Yazan LS, Ismail M (2011) Thymoquinone from Nigella sativa was more potent than cisplatin in eliminating of SiHa cells via apoptosis with down-regulation of Bcl-2 protein. Toxicol In Vitro 25(7):1392–1398CrossRefPubMed

37.

Norfazlina MN, Zuraina MYF, Rajab NF, Nazip SM, Rumiza AR, Zaila CFS, Mun LL et al (eds) (2014) Cytotoxicity study of Nigella sativa and Zingiber zerumbet extracts, thymoquinone and zerumbone isolated on human myeloid leukemia (HL60) cell. In: The Open Conference Proceedings Journal 4(2):99–107

38.

El-Najjar N, Chatila M, Moukadem H, Vuorela H, Ocker M, Gandesiri M et al (2010) Reactive oxygen species mediate thymoquinone-induced apoptosis and activate ERK and JNK signaling. Apoptosis 15(2):183–195CrossRefPubMed

39.

Gurung RL, Lim SN, Khaw AK, Soon JFF, Shenoy K, Ali SM et al (2010) Thymoquinone induces telomere shortening, DNA damage and apoptosis in human glioblastoma cells. PLoS ONE 5(8):121–124CrossRef

40.

Keizer H, Pinedo H, Schuurhuis G, Joenje H (1990) Doxorubicin (adriamycin): a critical review of free radical-dependent mechanisms of cytotoxicity. Pharmacol Ther 47(2):219–231CrossRefPubMed

41.

Czeczuga-Semeniuk E, Wolczynski S, Dabrowska M, Dzieciol J, Anchim T (2004) The effect of doxorubicin and retinoids on proliferation, necrosis and apoptosis in MCF-7 breast cancer cells. Folia Histochem Cytobiol 42(4):221–228PubMed

42.

Dirican A, Atmaca H, Bozkurt E, Erten C, Karaca B, Uslu R (2015) Novel combination of docetaxel and thymoquinone induces synergistic cytotoxicity and apoptosis in DU-145 human prostate cancer cells by modulating PI3K-AKT pathway. Clin Transl Oncol 17(2):145–151CrossRefPubMed

43.

Suwei W, Kotamraju S, Konorev E, Kalivendi S, Joseph J, Kalyanaraman B (2002) Activation of nuclear factor-κB during doxorubicin-induced apoptosis in endothelial cells and myocytes is pro-apoptotic: the role of hydrogen peroxide. Biochem J 367(3):729–740CrossRef

44.

Sakalar C, Yuruk M, Kaya T, Aytekin M, Kuk S, Canatan H (2013) Pronounced transcriptional regulation of apoptotic and TNF-NF-kappa-B signaling genes during the course of thymoquinone mediated apoptosis in HeLa cells. Mol Cell Biochem 383(1–2):243–251CrossRefPubMed

45.

46.

Koka PS, Mondal D, Schultz M, Abdel-Mageed AB, Agrawal KC (2010) Studies on molecular mechanisms of growth inhibitory effects of thymoquinone against prostate cancer cells: role of reactive oxygen species. Exp Biol Med 235(6):751–760CrossRef

47.

Paramasivam A, Sambantham S, Shabnam J, Raghunandhakumar S, Anandan B, Rajiv R et al (2012) Anti-cancer effects of thymoquinone in mouse neuroblastoma (Neuro-2a) cells through caspase-3 activation with down-regulation of XIAP. Toxicol Lett 213(2):151–159CrossRefPubMed

48.

Arafa E-SA, Zhu Q, Shah ZI, Wani G, Barakat BM, Racoma I et al (2011) Thymoquinone up-regulates PTEN expression and induces apoptosis in doxorubicin-resistant human breast cancer cells. Mutat Res Fundam Mol Mech Mutagen 706(1):28–35CrossRef

49.

Rooney S, Ryan M (2005) Modes of action of alpha-hederin and thymoquinone, active constituents of Nigella sativa, against HEp-2 cancer cells. Anticancer Res 25(6B):4255–4259PubMed

50.

Roepke M, Diestel A, Bajbouj K, Walluscheck D, Schonfeld P, Roessner A et al (2007) Lack of p53 augments thymoquinone-induced apoptosis and caspase activation in human osteosarcoma cells. Cancer Biol Ther 6(2):160–169CrossRefPubMed

51.

Hussain AR, Ahmed M, Ahmed S, Manogaran P, Platanias LC, Alvi SN et al (2011) Thymoquinone suppresses growth and induces apoptosis via generation of reactive oxygen species in primary effusion lymphoma. Free Radic Biol Med 50(8):978–987CrossRefPubMed

52.

Naus PJ, Henson R, Bleeker G, Wehbe H, Meng F, Patel T (2007) Tannic acid synergizes the cytotoxicity of chemotherapeutic drugs in human cholangiocarcinoma by modulating drug efflux pathways. J Hepatol 46(2):222–229CrossRefPubMed

Titel: Antiproliferative and Apoptosis-Inducing Activities of Thymoquinone in Lymphoblastic Leukemia Cell Line
verfasst von: Amin Soltani
Batoul Pourgheysari
Hedayatollah Shirzad
Zahra Sourani
Publikationsdatum: 08.12.2016
Verlag: Springer India
Erschienen in: Indian Journal of Hematology and Blood Transfusion / Ausgabe 4/2017
Print ISSN: 0971-4502
Elektronische ISSN: 0974-0449
DOI: https://doi.org/10.1007/s12288-016-0758-8

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