Login Register Cart 0
Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

In-Vitro Anti-Proliferative, Apoptotic and Antioxidative Activities of Medicinal Herb Kalonji (Nigella sativa)

Author(s): Tahir Maqbool, Sana J. Awan*, Sabeen Malik, Faheem Hadi, Somia Shehzadi and Kanza Tariq

Volume 20, Issue 15, 2019

Page: [1288 - 1308] Pages: 21

DOI: 10.2174/1389201020666190821144633

Price: $65

Abstract

Background: Natural product with apoptotic activity could serve as a potential new source for anti-cancer medicine. Numerous phytochemicals from plants have shown to exert antineoplastic effects via programmed cell death (apoptosis). Cancer is one of the leading causes of death in prosperous countries. The subject study was intended to evaluate the anticancer properties of Kalonji extracts against cancer cell lines HeLa and HepG2 and normal cell lines BHK and VERO were used as normal controls.

Materials & Methods: For the evaluation of anti-proliferative effects, cell viability and cell death in all groups of cells were evaluated via MTT, crystal violet and trypan blue assays. For the evaluation of angiogenesis, Immunocytochemistry and ELISA of VEGF were done. Immunocytochemistry and ELISA of Annexin-V and p53 were performed for the estimation of apoptosis in all groups of cells. Furthermore, LDH assay, antioxidant enzymes activity (GSH, APOX, CAT and SOD) and RT-PCR with proliferative and apoptotic markers along with internal control were also performed. Cancer cells of both cell lines HepG2 and HeLa cells showed reduced viability, angiogenesis and proliferation with increased apoptosis when treated with Kalonji extracts. Whereas anti-oxidative enzymes show enhanced levels in treated cancer cells as compared to untreated ones.

Conclusion: It was observed that Kalonji extracts have the ability to induce apoptosis and improve the antioxidant status of HeLa and HepG2 cells. They can also inhibit the proliferation and angiogenesis in both these cancer cell lines.

Keywords: Cancer, normal cells, kalonji, angiogenesis, apoptosis, anti-proliferation.

« Previous Next »
Graphical Abstract

[1]
Abd El-Wahab, A.E.; Ghareeb, D.A.; Sarhan, E.E.; Abu-Serie, M.M.; El Demellawy, M.A. In vitro biological assessment of Berberis vulgaris and its active constituent, berberine: Antioxidants, anti-acetylcholinesterase, anti-diabetic and anticancer effects. BMC Complement. Altern. Med., 2013, 13, 218-218.
[http://dx.doi.org/10.1186/1472-6882-13-218] [PMID: 24007270]
[2]
Chen, M.S.; Chen, D.; Dou, Q.P. Inhibition of proteasome activity by various fruits and vegetables is associated with cancer cell death. In Vivo, 2004, 18(1), 73-80.
[PMID: 15011755]
[3]
Cragg, G.M.; Newman, D.J. Plants as a source of anti-cancer agents. J. Ethnopharmacol., 2005, 100(1-2), 72-79.
[http://dx.doi.org/10.1016/j.jep.2005.05.011] [PMID: 16009521]
[4]
Tan, G.; Gyllenhaal, C.; Soejarto, D.D. Biodiversity as a source of anticancer drugs. Curr. Drug Targets, 2006, 7(3), 265-277.
[http://dx.doi.org/10.2174/138945006776054942] [PMID: 16515527]
[5]
Nader, M.A.; el-Agamy, D.S.; Suddek, G.M. Protective effects of propolis and thymoquinone on development of atherosclerosis in cholesterol-fed rabbits. Arch. Pharm. Res., 2010, 33(4), 637-643.
[http://dx.doi.org/10.1007/s12272-010-0420-1] [PMID: 20422375]
[6]
Kanter, M.; Akpolat, M.; Aktas, C. Protective effects of the volatile oil of Nigella sativa seeds on β-cell damage in streptozotocin-induced diabetic rats: A light and electron microscopic study. J. Mol. Histol., 2009, 40(5-6), 379-385.
[http://dx.doi.org/10.1007/s10735-009-9251-0] [PMID: 20049514]
[7]
Majdalawieh, A.F.; Fayyad, M.W. Recent advances on the anti-cancer properties of Nigella sativa, a widely used food additive. J. Ayurveda Integr. Med., 2016, 7(3), 173-180.
[http://dx.doi.org/10.1016/j.jaim.2016.07.004] [PMID: 27649635]
[8]
Kim, A. Mitochondria in cancer energy metabolism: Culprits or bystanders? Toxicol. Res., 2015, 31(4), 323-330.
[http://dx.doi.org/10.5487/TR.2015.31.4.323] [PMID: 26877834]
[9]
Xiao, S.; Zhou, Y.; Yi, W.; Luo, G.; Jiang, B.; Tian, Q.; Li, Y.; Xue, M. Fra-1 is downregulated in cervical cancer tissues and promotes cervical cancer cell apoptosis by p53 signaling pathway in vitro. Int. J. Oncol., 2015, 46(4), 1677-1684.
[http://dx.doi.org/10.3892/ijo.2015.2873] [PMID: 25651840]
[10]
El-Serag, H.B. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology, 2012, 142(6), 1264-1273.e1.
[http://dx.doi.org/10.1053/j.gastro.2011.12.061] [PMID: 22537432]
[11]
Sukowati, C.H.; El-Khobar, K.E.; Ie, S.I.; Anfuso, B.; Muljono, D.H.; Tiribelli, C. Significance of hepatitis virus infection in the oncogenic initiation of hepatocellular carcinoma. World J. Gastroenterol., 2016, 22(4), 1497-1512.
[http://dx.doi.org/10.3748/wjg.v22.i4.1497] [PMID: 26819517]
[12]
Wajid, N.; Naseem, R.; Anwar, S.S.; Awan, S.J.; Ali, M.; Javed, S.; Ali, F. The effect of gestational diabetes on proliferation capacity and viability of human umbilical cord-derived stromal cells. Cell Tissue Bank., 2015, 16(3), 389-397.
[http://dx.doi.org/10.1007/s10561-014-9483-4] [PMID: 25407535]
[13]
Shamim, S.; Rehman, A. Antioxidative enzyme profiling and biosorption ability of Cupriavidus metallidurans CH34 and Pseudomonas putida mt2 under cadmium stress. J. Basic Microbiol., 2015, 55(3), 374-381.
[http://dx.doi.org/10.1002/jobm.201300038] [PMID: 23832807]
[14]
Al-Oqail, M.M.; Farshori, N.N.; Al-Sheddi, E.S.; Musarrat, J.; Al-Khedhairy, A.A.; Siddiqui, M.A. In vitro cytotoxic activity of seed oil of fenugreek against various cancer cell lines. Asian Pac. J. Cancer Prev., 2013, 14(3), 1829-1832.
[http://dx.doi.org/10.7314/APJCP.2013.14.3.1829] [PMID: 23679282]
[15]
Al-Oqail, M.M.; Al-Sheddi, E.S.; Siddiqui, M.A.; Musarrat, J.; Al-Khedhairy, A.A.; Farshori, N.N. Anticancer activity of chloroform extract and sub-fractions of nepeta deflersiana on human breast and lung cancer cells: An in vitro cytotoxicity assessment. Pharmacogn. Mag., 2015, 11(Suppl. 4), S598-S605.
[http://dx.doi.org/10.4103/0973-1296.172968] [PMID: 27013801]
[16]
Al-Sheddi, E.S.; Farshori, N.N.; Al-Oqail, M.M.; Musarrat, J.; Al-Khedhairy, A.A.; Siddiqui, M.A. Cytotoxicity of Nigella sativa seed oil and extract against human lung cancer cell line. Asian Pac. J. Cancer Prev., 2014, 15(2), 983-987.
[http://dx.doi.org/10.7314/APJCP.2014.15.2.983] [PMID: 24568529]
[17]
Farshori, N.N.; Al-Sheddi, E.S.; Al-Oqail, M.M.; Musarrat, J.; Al-Khedhairy, A.A.; Siddiqui, M.A. Anticancer activity of Petroselinum sativum seed extracts on MCF-7 human breast cancer cells. Asian Pac. J. Cancer Prev., 2013, 14(10), 5719-5723.
[http://dx.doi.org/10.7314/APJCP.2013.14.10.5719] [PMID: 24289568]
[18]
Farshori, N.N.; Al-Sheddi, E.S.; Al-Oqail, M.M.; Musarrat, J.; Al-Khedhairy, A.A.; Siddiqui, M.A. Cytotoxicity assessments of Portulaca oleracea and Petroselinum sativum seed extracts on human hepatocellular carcinoma cells (HepG2). Asian Pac. J. Cancer Prev., 2014, 15(16), 6633-6638.
[http://dx.doi.org/10.7314/APJCP.2014.15.16.6633] [PMID: 25169500]
[19]
Pari, L.; Sankaranarayanan, C. Beneficial effects of thymoquinone on hepatic key enzymes in streptozotocin-nicotinamide induced diabetic rats. Life Sci., 2009, 85(23-26), 830-834.
[http://dx.doi.org/10.1016/j.lfs.2009.10.021] [PMID: 19903489]
[20]
Khattab, M.M.; Nagi, M.N. Thymoquinone supplementation attenuates hypertension and renal damage in nitric oxide deficient hypertensive rats. Phytother. Res., 2007, 21(5), 410-414.
[http://dx.doi.org/10.1002/ptr.2083] [PMID: 17236176]
[21]
Boskabady, M.H.; Mohsenpoor, N.; Takaloo, L. Antiasthmatic effect of Nigella sativa in airways of asthmatic patients. Phytomedicine, 2010, 17(10), 707-713.
[http://dx.doi.org/10.1016/j.phymed.2010.01.002] [PMID: 20149611]
[22]
Bayrak, O.; Bavbek, N.; Karatas, O.F.; Bayrak, R.; Catal, F.; Cimentepe, E.; Akbas, A.; Yildirim, E.; Unal, D.; Akcay, A. Nigella sativa protects against ischaemia/reperfusion injury in rat kidneys. Nephrol. Dial. Transplant., 2008, 23(7), 2206-2212.
[http://dx.doi.org/10.1093/ndt/gfm953] [PMID: 18211980]
[23]
Ragheb, A.; Attia, A.; Eldin, W.S.; Elbarbry, F.; Gazarin, S.; Shoker, A. The protective effect of thymoquinone, an anti-oxidant and anti-inflammatory agent, against renal injury: A review. Saudi J. Kidney Dis. Transpl., 2009, 20(5), 741-752.
[PMID: 19736468]
[24]
Randhawa, M.A.; Alghamdi, M.S. Anticancer activity of Nigella sativa (black seed) - a review. Am. J. Chin. Med., 2011, 39(6), 1075-1091.
[http://dx.doi.org/10.1142/S0192415X1100941X] [PMID: 22083982]
[25]
Heydari, A. ali Tavakoli, M.; Salim, N.; Heydari, Z. Detection of review spam: A survey. Expert Syst. Appl., 2015, 42(7), 3634-3642.
[http://dx.doi.org/10.1016/j.eswa.2014.12.029]
[26]
Manosroi, J.; Dhumtanom, P.; Manosroi, A. Anti-proliferative activity of essential oil extracted from Thai medicinal plants on KB and P388 cell lines. Cancer Lett., 2006, 235(1), 114-120.
[http://dx.doi.org/10.1016/j.canlet.2005.04.021] [PMID: 15979235]
[27]
Rahmani-Nezhad, S.; Safavi, M.; Pordeli, M.; Ardestani, S.K.; Khosravani, L.; Pourshojaei, Y.; Mahdavi, M.; Emami, S.; Foroumadi, A.; Shafiee, A. Synthesis, in vitro cytotoxicity and apoptosis inducing study of 2-aryl-3-nitro-2H-chromene derivatives as potent anti-breast cancer agents. Eur. J. Med. Chem., 2014, 86, 562-569.
[http://dx.doi.org/10.1016/j.ejmech.2014.09.017] [PMID: 25216378]
[28]
Tunjung, W.A.S.; Cinatl, J., Jr; Michaelis, M.; Smales, C.M. Anti-cancer effect of kaffir lime (Citrus hystrix DC) leaf extract in cervical cancer and neuroblastoma cell lines. Procedia Chem., 2015, 14, 465-468.
[http://dx.doi.org/10.1016/j.proche.2015.03.062]
[29]
Ramakrishnan, S.; Subramanian, I.V.; Yokoyama, Y.; Geller, M. Angiogenesis in normal and neoplastic ovaries. Angiogenesis, 2005, 8(2), 169-182.
[http://dx.doi.org/10.1007/s10456-005-9001-1] [PMID: 16211363]
[30]
Ferrara, N. Vascular endothelial growth factor as a target for anticancer therapy. Oncologist, 2004, 9(Suppl. 1), 2-10.
[http://dx.doi.org/10.1634/theoncologist.9-suppl_1-2] [PMID: 15178810]
[31]
Greenberg, J.I.; Cheresh, D.A. VEGF as an inhibitor of tumor vessel maturation: Implications for cancer therapy. Expert Opin. Biol. Ther., 2009, 9(11), 1347-1356.
[http://dx.doi.org/10.1517/14712590903208883] [PMID: 19761418]
[32]
Duyndam, M.C.; Hilhorst, M.C.; Schlüper, H.M.; Verheul, H.M.; van Diest, P.J.; Kraal, G.; Pinedo, H.M.; Boven, E. Vascular endothelial growth factor-165 overexpression stimulates angiogenesis and induces cyst formation and macrophage infiltration in human ovarian cancer xenografts. Am. J. Pathol., 2002, 160(2), 537-548.
[http://dx.doi.org/10.1016/S0002-9440(10)64873-0] [PMID: 11839574]
[33]
Hefler, L.A.; Mustea, A.; Könsgen, D.; Concin, N.; Tanner, B.; Strick, R.; Heinze, G.; Grimm, C.; Schuster, E.; Tempfer, C.; Reinthaller, A.; Zeillinger, R. Vascular endothelial growth factor gene polymorphisms are associated with prognosis in ovarian cancer. Clin. Cancer Res., 2007, 13(3), 898-901.
[http://dx.doi.org/10.1158/1078-0432.CCR-06-1008] [PMID: 17289883]
[34]
Choedon, T.; Dolma, D.; Mathan, G.; Kumar, V. Molecular insights into the anti-cancer properties of traditional Tibetan medicine Yukyung Karne. BMC Complement. Altern. Med., 2014, 14(1), 380.
[http://dx.doi.org/10.1186/1472-6882-14-380] [PMID: 25292320]
[35]
Zhang, T-T.; Yang, L.; Jiang, J-G. Effects of thonningianin A in natural foods on apoptosis and cell cycle arrest of HepG-2 human hepatocellular carcinoma cells. Food Funct., 2015, 6(8), 2588-2597.
[http://dx.doi.org/10.1039/C5FO00388A] [PMID: 26119846]
[36]
Elmore, S. Apoptosis: A review of programmed cell death. Toxicol. Pathol., 2007, 35(4), 495-516.
[http://dx.doi.org/10.1080/01926230701320337] [PMID: 17562483]
[37]
Fadeel, B.; Orrenius, S. Apoptosis: A basic biological phenomenon with wide-ranging implications in human disease. J. Intern. Med., 2005, 258(6), 479-517.
[http://dx.doi.org/10.1111/j.1365-2796.2005.01570.x] [PMID: 16313474]
[38]
Ovadje, P.; Ma, D.; Tremblay, P.; Roma, A.; Steckle, M.; Guerrero, J-A.; Arnason, J.T.; Pandey, S. Evaluation of the efficacy & biochemical mechanism of cell death induction by Piper longum extract selectively in in-vitro and in-vivo models of human cancer cells. PLoS One, 2014, 9(11)e113250
[http://dx.doi.org/10.1371/journal.pone.0113250] [PMID: 25401766]
[39]
Hostanska, K.; Nisslein, T.; Freudenstein, J.; Reichling, J.; Saller, R. Cimicifuga racemosa extract inhibits proliferation of estrogen receptor-positive and negative human breast carcinoma cell lines by induction of apoptosis. Breast Cancer Res. Treat., 2004, 84(2), 151-160.
[http://dx.doi.org/10.1023/B:BREA.0000018413.98636.80] [PMID: 14999145]
[40]
Warin, R.F.; Chen, H.; Soroka, D.N.; Zhu, Y.; Sang, S. Induction of lung cancer cell apoptosis through a p53 pathway by [6]-shogaol and its cysteine-conjugated metabolite M2. J. Agric. Food Chem., 2014, 62(6), 1352-1362.
[http://dx.doi.org/10.1021/jf405573e] [PMID: 24446736]
[41]
Plackal Adimuriyil George, B.; Tynga, I.M.; Abrahamse, H. In vitro antiproliferative effect of the acetone extract of Rubus fairholmianus gard. BioMed Res. Int., 2015, 2015165037
[http://dx.doi.org/10.1155/2015/165037] [PMID: 26078938]
[42]
Saad, B.; Dakwar, S.; Said, O.; Abu-Hijleh, G.; Al Battah, F.; Kmeel, A.; Aziazeh, H. Evaluation of medicinal plant hepatotoxicity in co-cultures of hepatocytes and monocytes. Evid. Based Complement. Alternat. Med., 2006, 3(1), 93-98.
[http://dx.doi.org/10.1093/ecam/nel002] [PMID: 16550229]
[43]
Bailey, K.M.; Wojtkowiak, J.W.; Hashim, A.I.; Gillies, R.J. Targeting the metabolic microenvironment of tumors. Adv. Pharmacol., 2012, 65, 63-107.
[44]
Lendahl, U.; Lee, K.L.; Yang, H.; Poellinger, L. Generating specificity and diversity in the transcriptional response to hypoxia. Nat. Rev. Genet., 2009, 10(12), 821-832.
[http://dx.doi.org/10.1038/nrg2665] [PMID: 19884889]
[45]
Toyokuni, S. Molecular mechanisms of oxidative stress-induced carcinogenesis: From epidemiology to oxygenomics. IUBMB Life, 2008, 60(7), 441-447.
[http://dx.doi.org/10.1002/iub.61] [PMID: 18465793]
[46]
Anastasiou, D.; Poulogiannis, G.; Asara, J.M.; Boxer, M.B.; Jiang, J.K.; Shen, M.; Bellinger, G.; Sasaki, A.T.; Locasale, J.W.; Auld, D.S.; Thomas, C.J.; Vander Heiden, M.G.; Cantley, L.C. Inhibition of pyruvate kinase M2 by reactive oxygen species contributes to cellular antioxidant responses. Science, 2011, 334(6060), 1278-1283.
[http://dx.doi.org/10.1126/science.1211485] [PMID: 22052977]
[47]
Fuchs-Tarlovsky, V. Role of antioxidants in cancer therapy. Nutrition, 2013, 29(1), 15-21.
[http://dx.doi.org/10.1016/j.nut.2012.02.014] [PMID: 22784609]

Rights & Permissions Print Cite
Article Metrics
32
3
1
1
© 2024 Bentham Science Publishers | Privacy Policy