Skip to main content
Top
Published in: Indian Journal of Hematology and Blood Transfusion 4/2017

01-12-2017 | Original Article

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

Authors: Amin Soltani, Batoul Pourgheysari, Hedayatollah Shirzad, Zahra Sourani

Published in: Indian Journal of Hematology and Blood Transfusion | Issue 4/2017

Login to get access

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.
Literature
1.
go back to reference 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 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
2.
go back to reference Pyatt D, Hays S (2010) A review of the potential association between childhood leukemia and benzene. Chem Biol Interact 184(1):151–164CrossRefPubMed Pyatt D, Hays S (2010) A review of the potential association between childhood leukemia and benzene. Chem Biol Interact 184(1):151–164CrossRefPubMed
3.
go back to reference Narayanan S, Shami PJ (2012) Treatment of acute lymphoblastic leukemia in adults. Crit Rev Oncol Hematol 81(1):94–102CrossRefPubMed Narayanan S, Shami PJ (2012) Treatment of acute lymphoblastic leukemia in adults. Crit Rev Oncol Hematol 81(1):94–102CrossRefPubMed
4.
go back to reference 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 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
5.
go back to reference Roti G, Stegmaier K (2014) New approaches to target T-ALL. Front Oncol 4:201–211CrossRef Roti G, Stegmaier K (2014) New approaches to target T-ALL. Front Oncol 4:201–211CrossRef
6.
go back to reference 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 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
7.
go back to reference 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 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
8.
go back to reference Woo CC, Kumar AP, Sethi G, Tan KHB (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83(4):443–451CrossRefPubMed Woo CC, Kumar AP, Sethi G, Tan KHB (2012) Thymoquinone: potential cure for inflammatory disorders and cancer. Biochem Pharmacol 83(4):443–451CrossRefPubMed
9.
go back to reference Abel-Salam BK (2012) Immunomodulatory effects of black seeds and garlic on alloxan-induced diabetes in albino rat. Allergol Immunopathol 40(6):336–340CrossRef 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Womack K, Anderson M, Tucci M, Hamadain E, Benghuzzi H (2005) Evaluation of bioflavonoids as potential chemotherapeutic agents. Biomed Sci Instrum 42:464–469 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Goldsworthy TL, Conolly RB, Fransson-Steen R (1996) Apoptosis and cancer risk assessment. Mutat Res Rev Genet 365(1):71–90CrossRef Goldsworthy TL, Conolly RB, Fransson-Steen R (1996) Apoptosis and cancer risk assessment. Mutat Res Rev Genet 365(1):71–90CrossRef
22.
go back to reference Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10(2):86–103CrossRefPubMedPubMedCentral Ciocca DR, Calderwood SK (2005) Heat shock proteins in cancer: diagnostic, prognostic, predictive, and treatment implications. Cell Stress Chaperones 10(2):86–103CrossRefPubMedPubMedCentral
23.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Bauer J, Wekerle H, Lassmann H (1995) Apoptosis in brain-specific autoimmune disease. Curr Opin Immunol 7(6):839–843CrossRefPubMed Bauer J, Wekerle H, Lassmann H (1995) Apoptosis in brain-specific autoimmune disease. Curr Opin Immunol 7(6):839–843CrossRefPubMed
28.
go back to reference 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 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.
go back to reference 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 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.
go back to reference Effenberger-Neidnicht K, Schobert R (2011) Combinatorial effects of thymoquinone on the anti-cancer activity of doxorubicin. Cancer Chemother Pharmacol 67(4):867–874CrossRefPubMed 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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
46.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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.
go back to reference 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 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
Metadata
Title
Antiproliferative and Apoptosis-Inducing Activities of Thymoquinone in Lymphoblastic Leukemia Cell Line
Authors
Amin Soltani
Batoul Pourgheysari
Hedayatollah Shirzad
Zahra Sourani
Publication date
01-12-2017
Publisher
Springer India
Published in
Indian Journal of Hematology and Blood Transfusion / Issue 4/2017
Print ISSN: 0971-4502
Electronic ISSN: 0974-0449
DOI
https://doi.org/10.1007/s12288-016-0758-8

Other articles of this Issue 4/2017

Indian Journal of Hematology and Blood Transfusion 4/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine