Black Cumin Seeds Extract Increase Lymphocyte Activity in IFN-γ Secretion in Sprague Dawley Rat (SD) Induced by Dimethylbenzantracene

Akrom Akrom, Titiek Hidayati, Sagiran Sagiran, Indrayanti Indrayanti

Abstract


Interferon-gamma (IFN-γ) is one of the central cytokines in the anti-carcinogenesis immune response. Black cumin seeds (BCS) have an active content of thymoquinone and unsaturated fatty acids with biological activity as immunomodulators. This study aimed to determine the effect of administration of BCS extract on IFN-γ secretion activity by DMBA-induced SD rat lymphocytes. In vivo experimental study on DMBA-induced SD rats, BCS extract was given with three doses for two weeks before being induced and five weeks during DMBA induction. IFN-γ levels in lymphocyte culture supernatants were determined by the ELISA method. The difference in IFN-γ levels between groups was analyzed by ANOVA test, the significance of 95%. The results showed that administration of BCS extract for 14 days did not affect cellular composition toward the edge of the test animal. BCS extract can increase IFN-γ secretion activity by DMBA-induced SD rat lymphocytes.

Keywords: black cumin seed, IFN-γ; DMBA: immunomodulator, carcinogenesis.


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Akrom, A. and Darmawan, E., 2017, Tolerability and safety of black cumin seed oil (Bcso) administration for 20 days in healthy subjects, Biomedical Research (India), 28(9), 4196-4201.

Akrom, A. and Mustofa, 2017, Black cumin seed oil increases phagocytic activity and secretion of IL-12 by macrophages, Biomedical Research (India), 28(12), 5241-5245.

Al-Ghamdi, M.S., 2002, The anti-inflammatory, analgesic and antipyretic activity of Nigella sativa, Journal of Ethnopharmacology, 76(1), 45-48.

American Cancer Society, 2016, Cancer Facts, Cancer Facts, 1–9. CrossRef

Badr, G., Lefevre, E.A. and Mohany, M., 2011, Thymoquinone inhibits the CXCL12-induced chemotaxis of multiple myeloma cells and increases their susceptibility to fas-mediated apoptosis, PLoS ONE, 6(9). CrossRef

Baj-Krzyworzeka, M., Baran, J., Szatanek, R., Stankiewicz, D., Siedlar, M. and Zembala, M., 2004, Prevention and reversal of tumor cell-induced monocyte deactivation by cytokines, purified protein derivative (PPD) and anti-IL-10 antibody, Cancer Immunity, 4, 8.

Ballestero Fêo, H., Flórez, L.M., Yamatogi, R.S., Duzanski, A.P., Araújo Jr., J.P., Oliveira, R.A. and Rocha, N.S., 2018, Does the tumour microenvironment alter tumorigenesis and clinical response in transmissible venereal tumour in dogs?, Vet Comp Oncol, 16(3), 370–378.

Barletta, E., Gorini, E., Vinels, P., Miligi, L., Davico, L., Mugnai, G., Ciolli, S., Leoni, F., Bertini, M., Matullo, G. and Costantini, A.S., 2004, Ras gene mutations in patients with acute myeloid leukemia and exposure to chemical agents, Carcinogenesis, 25(5), 749–755.

Buters, J., Quintanilla-Martinez, L., Schober, W., Soballa, V.J., Hintermair, J., Wolff, T., Gonzalez, F.J. and Greim, H., 2003, CYP1B1 determines susceptibility to low doses of 7,12-dimethylbenz[a]anthracene-induced ovarian cancers in mice: Correlation of CYP1B1-mediated DNA adducts with carcinogenicity, Carcinogenesis, 24(2), 327–334. CrossRef

Castro, F., Cardoso, A.P., Gonçalves, R.M., Serre, K., and Oliveira, M.J., 2018, Interferon-gamma at the crossroads of tumor immune surveillance or evasion, Frontiers in Immunology, 9, 1–19. CrossRef

Dembic, Z., 2015, The Cytokines of the Immune System: The Role of Cytokines in Disease Related to Immune Response, 1st Edition, elsevier: Academic Press. CrossRef

Disis, M.L., 2010, Immune regulation of cancer, Journal of Clinical Oncology, 28(29), 4531-4538. CrossRef

Dunn, G.P., Old, L.J. and Schreiber, R.D., 2004, The immunobiology of cancer immunosurveillance and immunoediting, Immunity, 21(2), 137–148. CrossRef

El-Mahmoudy, A., Matsuyama, H., Borgan, M.A., Shimizu, Y., El-Sayed, M.G., Minamoto, N. and Takewaki, T., 2002, Thymoquinone suppresses expression of inducible nitric oxide synthase in rat macrophages, International Immunopharmacology, 2(11), 1603–1611. CrossRef

el-Aziz, M.A., Hassan, H.A., Mohammed, M.H., Meki, A., Abdel-Ghaffar, S.K. and Hussein, M.R., 2005, The biochemical and morphological alterations following administration of melatonin, retinoic acid and Nigella sativa in mammary carcinoma:an animal model, Int. J. Exp Pathol., 86(6), 383–396.

Fajar, D.R., Akrom and Darmawan, E., 2017, The influence of black cumin seed oil therapy with dosage of 1.5 mL/day and 3 mL/day to interleukin-21 (IL-21) expression of the patients with metabolic syndrome risk, IOP Conference Series: Materials Science and Engineering, 259(1), 012012. CrossRef

Fathy, M. and Nikaido, T., 2013, In vivo modulation of iNOS pathway in hepatocellular carcinoma by Nigella sativa, Environ Health Prev Med., 18(5), 377–385.

Gao, J., Mitchell, L.A., Lauer, F.T., Burchiel, S.W., 2008, p53 and ATM/ATR regulate 7,12-dimethylbenz[a]anthracene-induced immunosuppression, Mol. Pharmacol., 73(1), 137–146.

Hayakawa, Y., Takeda, K., Yagita, H., Smyth, M.J., Van Kaer, L., Okumura, K. and Saiki, I, 2002, IFN-γ-mediated inhibition of tumor angiogenesis by natural killer T-cell ligand, α-galactosylceramide, Blood, 100(5), 1728–1733.

Hidayati, T., A. (2006). Effect of ethanol extract of black cumin on phagocytic activity of macrophages of Swiss P.berghei infected mice in vitro, Proceedings of the national seminar on pharmacotherapy. Proceedings of the National Seminar on Pharmacotherapy. Yogyakarta: Professional Program of Pharmacy Faculty of UAD Pharmacy, Yogyakarta: January 14, 2006.

Hidayati, T., Akrom, Indrayanti, and Sagiran, 2017, Evaluation of the Black Cumin Seed Oil Role (BCSO) on a Decline in eNOS Expression and Plasma NO Levels: Initial Studies Kemopreventive BCSO for Lung Cancer, International Journal of Bioscience, Biochemistry and Bioinformatics, 7(3), 162–168. CrossRef

Hidayati, T., Akrom, Indrayanti, and Sagiran, 2019, Chemopreventive effect of black cumin seed oil (BCSO) by increasing p53 expression in dimethylbenzanthracene (DMBA)-induced Sprague Dawley rats, Research Journal of Chemistry and Environment, 23(8), 24-32.

Ichihara, F., Kono, K., Takahashi, A., Kawaida, H., Sugai, H. and Fujii, H., 2003, Increased populations of regulatory T cells in peripheral blood and tumor-infiltrating lymphocytes in patients with gastric and esophageal cancers, Clinical Cancer Research, 9(12), 4404–4408.

Karimi, G., Aghasizadeh, M., Razavi, M. and Taghiabadi, E., 2011, Protective effects of aqueous and ethanolic extracts of Nigella sativa L. and Portulaca oleracea L. on free radical induced hemolysis of RBCs, DARU, Journal of Pharmaceutical Sciences, 19(4), 295–300.

Li, J.H., Kluger, M.S., Madge, L.A., Zheng, L., Bothwell, A.L. and Pober, J.S., 2002, Interferon-γ augments CD95(APO-1/Fas) and pro-caspase-8 expression and sensitizes human vascular endothelial cells to CD95-mediated apoptosis, American Journal of Pathology, 161(4), 1485–1495. CrossRef

Mollazadeh, H., Afshari, A.R. and Hosseinzadeh, H., 2017, Review on the Potential Therapeutic Roles of Nigella sativa in the Treatment of Patients with Cancer: Involvement of Apoptosis: - Black cumin and cancer, J Pharmacopuncture, 20(3), 158–172.

Musa, D., Dilsiz, N., Gumushan, H., Ulakoglu, G. and Bitiren, M., 2004, Antitumor activity of an ethanol extract of Nigella sativa seeds, Biologia-Bratislava, 59(6), 735–740.

N’jai, A.U., Larsen, M., Shi, L., Jefcoate, C.R. and Czuprynski, C.J., 2010, Bone marrow lymphoid and myeloid progenitor cells are suppressed in 7,12-dimethylbenz(a)anthracene (DMBA) treated mice, Toxicology, 271(1–2), 27–35.

Odhaib, K.J., Adeyemi, K.D., Ahmed, M.A., Jahromi, M.F., Jusoh, S., Samsudin, A.A., Alimon, A.R., Yaakub, H. and Sazili, A.Q., 2018, Influence of Nigella sativa seeds, Rosmarinus officinalis leaves and their combination on growth performance, immune response and rumen metabolism in Dorper lambs. Trop Anim Health Prod., 50(5), 1011–1023.

Parmar, J., Sharma, P., Verma, P., Sharma, P. and Goyal, P.K., 2011, Modulation of DMBA- induced biochemical and histopathological changes by Syzygium cumini seed extract during skin carcinogenesis, Int J Cur Biomed Phar Res., 1(2), 24–30.

Rachman, P.N.R., Akrom, A. and Darmawan, E., 2017, The efficacy of black cumin seed (Nigella sativa) oil and hypoglycemic drug combination to reduce HbA1c level in patients with metabolic syndrome risk, IOP Conference Series: Materials Science and Engineering, 259(1), 012018. CrossRef

Randhawa, M.A. and Alghamdi, M.S., 2011, Anticancer activity of Nigella sativa (Black Seed)-A review, The American Journal of Chinese Medicine, 39(6), 1075–1091. CrossRef

Ren, W., Li, Y, Xia, X., Guo, W., Zhai, T., Jin, Y., Che, Y., Gao, H., Duan, X., Ma, H., Huang, T., Huang, J. and Lei, L., 2018, Arginine inhibits the malignant transformation induced by interferon- gamma through the NF-κB-GCN2/eIF2α signaling pathway in mammary epithelial cells in vitro and in vivo, Exp Cell Res., 368(2), 236–247.

Ren, W.B., Xia, X.J., Huang, J., Guo, W.F., Che, Y.Y., Huang, T.H. and Lei, L.C., 2019, Interferon-γ regulates cell malignant growth via the c-Abl/HDAC2 signaling pathway in mammary epithelial cells, J Zhejiang Univ Sci B., 20(1), 39–48.

Selinger, E. and Reiniš, M., 2018, Epigenetic View on Interferon γ Signalling in Tumour Cells, Folia Biol., 64(4), 125–136.

Shaterzadeh-Yazdi, H., Noorbakhsh, M.F., Hayati, F., Samarghandian, S, Farkhondeh, T., 2018, Immunomodulatory and Anti-inflammatory Effects of Thymoquinone, Cardiovasc Hematol. Disord Drug Targets., 18(1), 52–60.

Soliman, E.S., Hamad, R.T. and Ahmed, A., 2017, Prophylactic and immune modulatory influences of Nigella sativa Linn. in broilers exposed to biological challenge, Vet World, 10(12), 1447–1455.

Upadhyay, S., Sharma, N., Gupta, K.B., and Dhiman, M., 2018, Role of immune system in tumor progression and carcinogenesis, J Cell Biochem, 119(7), 5028–5042.

Xiao, M., Wang, C., Zhang, J., Li, Z., Zhao, X., and Qin, Z., 2009, IFNgamma; promotes papilloma development by up-regulating th17-associated inflammation, Cancer Research, 69(5), 2010–2017. CrossRef

Zekri, A.N., El Deeb, S., Bahnassy, A.A., Badr, A.M., Abdellateif, M.S., Esmat, G., Salama, H., Mohanad, M., El-Dien, A.E. and Rabah, S.A.E.A., 2018, Role of relevant immune-modulators and cytokines in hepatocellular carcinoma and premalignant hepatic lesions, World J Gastroenterol, 24(11), 1228–1238.




DOI: http://dx.doi.org/10.14499/indonesianjcanchemoprev10iss3pp140-148

Copyright (c) 2019 Akrom Akrom, Titiek Hidayati, Sagiran Sagiran, Indrayanti Indrayanti

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Indonesian Society for Cancer Chemoprevention