Angiogenesis, Inflammation & Therapeutics | Online ISSN  2207-872X
RESEARCH ARTICLE   (Open Access)

Extract of Urgenia grandiflora inhibited breast cancer cell (MCF-7) proliferation and tumorgenesity

Ibrahim B. E. El Bashir A,B, Loiy Elsir Ahmed HassanC, Amin M. S. Abdul Majid D, Sakina Yagi A*

+ Author Affiliations

Journal of Angiotherapy 3(1) 138-146 https://doi.org/10.25163/angiotherapy.3120821273031119

Submitted: 27 July 2019  Revised: 30 October 2019  Published: 03 November 2019 

Abstract

Objective: To investigate the cytotoxicity of Urgenia grandiflora bulbs towards three cancer cell lines; human colorectal carcinoma cell line (HCT 116), human hormone sensitive and invasive breast cancer cell line (MCF-7) and human hormone resistant breast cancer cell line (MDA-MB-231), in addition to endothelial normal EA.hy926 cell line. According to selective antiproliferative effect against MCF-7 breast cancer, U. grandiflora extract was subjected to apoptosis and antitumorgenesity studies on MCF-7 cell line. Methods: Maceration with chloroform: methanol (1:1, v/v) was performed to obtain crude extract. Cytotoxicity was established by colorimetric measurement of cell viability. The effect of the extract on mitochondrial membrane potential, chromatin condensation and nuclear morphology of MCF-7 cells were evaluated using Hoechst 33342 stain. The antitumorgenesity was also determined by evaluation of the ability of extract to suppress the reproductive potential of cell division and colonization after treatment (colongenicity). The effect of extract on migration of tumor cells from their primary growth site to distant locations was evaluated by the wound healing assay. Effect of extract on invasion of matrigel by MCF-7 cells was evaluated using standard methods. Results: U. grandiflora extract showed tumor-specific antiproliferative activity against MCF-7 cells. the extract was also found to exert some toxicity towards the normal cell line EA.hy926 and this could be more likely attributed to its richness in cardiac glycosides. The extract demonstrated programmed cell death features, as it induced cell condensation, membrane flubbing and DNA fragmentation, also it disrupted mitochondria integrity in treated cells. Moreover the extract profoundly inhibited tumorgenisity of MCF-7 via inhibition of cell migration colony formation and cell invasion. Conclusion: U. grandiflora could be a new source of chemotherapeutic for breast cancer.

Key words: Urgenia grandiflora, anticancer, apoptosis, antitumorgenesis in vitro

Public Interest Statement: Ureginea grandiflora has a potential chemotherapeutic effect against breast cancer 

References

Ahmed HG, Eltom FM, Doumi MA, Eltybe MM, Mahmoud TA, Ebnoof EA, Salih RA. (2014). Burden of Cancer in North Sudan: A community-based Survey; Egypt. Acad J Biolog Sci; 6(2): 55- 63.
https://doi.org/10.21608/eajbsc.2014.16030
 
Almeida CA., 2010. Cancer: basic science and clinical aspects. Wiley-Blackwell, London.
 
Al Dhaheri Y, Attoub S, Arafat K, AbuQamar S, Viallet J, Saleh A, Al Agha H, Eid A, Iratn R. (2013). Anti-metastatic and anti-tumor growth effects of Origanum majorana on highly metastatic human breast cancer cells: inhibition of NFκB signaling and reduction of nitric oxide production. PLoS ONE; 8(7): e68808.
https://doi.org/10.1371/journal.pone.0068808
PMid:23874773 PMCid:PMC3707896
 
Andrews FW. (1956). The Flowering Plants of the Sudan: Volume III (Compositae-Gramineae) T. Buncle & Co., Ltd,
 
Babula P, Masarik M, Adam V, Provaznik I, Kizek R. (2013). From Na+ /K+-ATPase and cardiac glycosides to cytotoxicity and cancer treatment. Anti-Cancer Agents Med Chem; 13(7): 1069 - 1087.
https://doi.org/10.2174/18715206113139990304
PMid:23537048
 
Baharetha HM. (2012). The use of Nigella sativa Linn. supercritical carbon dioxide extract for breast cancer herapy by targeting the angiogenesis cascade. Msc Thesis, USM.
 
Balunas MJ, Kinghorn ADI. (2005). Drug discovery from medicinal plants. Life Sci; 78: 431-441.
https://doi.org/10.1016/j.lfs.2005.09.012
PMid:16198377
 
Bockhorn M, Jain RK, Munn LL. (2007). Active versus passive mechanisms in metastasis: do cancer cells crawl into vessels, or are they pushed? Lancet Oncol; 8: 444-448.
https://doi.org/10.1016/S1470-2045(07)70140-7
 
Bray F, Ren JS, Masuyer E, Ferlay J. (2013). Global estimates of cancer prevalence for 27 sites in the adult population in 2008. Int J Cancer; 132(5): 1133-45.
https://doi.org/10.1002/ijc.27711
PMid:22752881
 
Calderón-Montaño JM, Burgos-Morón E, Luis Orta M, Maldonado-Navas D, García-Domínguez I, López-Lázaro M. (2014). Evaluating the cancer therapeutic potential of cardiac glycosides. Bio Med Res Int; Article ID 794930, 9 pages.
https://doi.org/10.1155/2014/794930
PMid:24895612 PMCid:PMC4033509
 
Cragg GM, Newmann DJ. (2005). Plants as source of anticancer agents. J. Ethnopharmacol; 100: 72-79.
https://doi.org/10.1016/j.jep.2005.05.011
PMid:16009521
 
De S, Banerjee S, Babu MN, Lakhmi BM, Babu TMS. (2016). Review on Cardiac glycosides in cancer research and cancer therapy. Indo Amer J Pharmaceut Res; 6(05).
 
Elebead FM, Hamid A, Hilmi HS, Galal H. (2012). Mapping cancer disease using geographical information system (GIS) in Gezira State-Sudan. J Community Health; 37(4): 830-9.
https://doi.org/10.1007/s10900-011-9517-9
PMid:22227773
 
Elamin A, Ibrahim ME, Abuidris D, Mohamed KEH, Mohammed SI. (2015). Part I: cancer in Sudan-burden, distribution, and trends breast, gynecological, and prostate cancers. Cancer Medicine; 4(3): 447-456.
https://doi.org/10.1002/cam4.378
PMid:25641872 PMCid:PMC4380970
 
Eguchi K. (2001). Apoptosis in autoimmune diseases. Intern Med; 40: 275-284.
https://doi.org/10.2169/internalmedicine.40.275
PMid:11334384
 
El-Seedi HR, Burman R, Mansour A, Turki Z, Boulos L, Gullbo J, Göransson U. 2013The traditional medical uses and cytotoxic activities of sixty-one Egyptian plants: Discovery of an active cardiac glycoside from Urginea maritima. J. Ethnopharmacol; 145: 746-757.
https://doi.org/10.1016/j.jep.2012.12.007
PMid:23228916
 
Felth J, Rickardson L, Rosén J, Wickstroõm M, Fryknas M, Lindskog M, Bohlin L, Gullbo J. (2009). Cytotoxic effects of cardiac glycosides in colon cancer cells, alone and in combination with standard chemotherapeutic drugs. J Nat Prod; 72: 1969-1974.
https://doi.org/10.1021/np900210m
PMid:19894733
 
Franken NP, Rodermond H, Stap J, Haveman J, Bree C. Clonogenic assay of cells in vitro. Nat Protoc 2006; 1(5): 2315-2319.
https://doi.org/10.1038/nprot.2006.339
PMid:17406473
 
Foo J, Michor F. Evolution of acquired resistance to anti-cancer therapy. (2014). J Theor Biol; 355: 10-20
https://doi.org/10.1016/j.jtbi.2014.02.025
PMid:24681298 PMCid:PMC4058397
 
Harborne Jb. (1984). Phytochemical Methods. 2nd edition, Springer; p 37-99.
https://doi.org/10.1007/978-94-009-5570-7_2
 
Hartwell JL. (1982). Plants Used Against Cancer. Quarterman, Lawrence, MA.
 
Johnson L, Walsh M, Chen L. (1980). Localization of mitochondria in living cells with rhodamine 123. Proc Natl Acad Sci; 77: 990-994.
https://doi.org/10.1073/pnas.77.2.990
PMid:6965798 PMCid:PMC348409
 
Kepp O, Menger L, Vacchelli E, Adjemian S, Martins I, Ma Y, Sukkurwala A, Michaud M, Galluzzi L, Zitvogel L, Kroemer G. (2012). Anticancer activity of cardiac glycosides: At the frontier between cell-autonomous and immunological effects. Oncoimmunology; 1(9): 1640-1642.
https://doi.org/10.4161/onci.21684
PMid:23264921 PMCid:PMC3525630
 
Liang CC, Park A, Guan JL. (2007). In vitro scratch assay: a convenient and inexpensive method for analysis of cell migration in vitro. Nat Protoc; 2(2): 329-333.
https://doi.org/10.1016/j.tiv.2007.04.005
PMid:17560072
 
Lombardi VRM, Carrera I, Cacabelos R. (2017). In vitro screening for cytotoxic activity of herbal extracts. Evid Based Complementary Altern Med; Article ID 2675631: 8 pages.
https://doi.org/10.1155/2017/2675631
PMid:28386288 PMCid:PMC5366791
 
Mosmann T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunological Methods; 65: 55-63.
https://doi.org/10.1016/0022-1759(83)90303-4
 
Nath R, Roy S, De B, Choudhury MD. (2013). Anticancer and antioxidant activity of croton: A review. Int J Pharm Sci; 5: 63-70.
 
Newman DJ, Cragg GM. (2007). Natural products as sources of new drugs over the last 25 years. J Nat Prod; 70:461-477.
https://doi.org/10.1021/np068054v
PMid:17309302
 
Newman RA, Yang P, Pawlus AD, Block KI. (2008). Cardiac glycosides as novel cancer therapeutic agents. Mol Interv; 8(1): 36-49.
https://doi.org/10.1124/mi.8.1.8
PMid:18332483
 
Oberhammer FA, Hochegger K, Froschl G, Tiefenbacher R, Pavelka M. (1994). Chromatin condensation during apoptosis is accompanied by degradation of lamin A+B, without enhanced activation of Cdc2 kinase. J Cell Biol; 126: 827-37.
https://doi.org/10.1083/jcb.126.4.827
PMid:8051209 PMCid:PMC2120132
 
O'Connor JE, Vargas JL, Kimler BF, Hernandez-Yago J, Grisolia S. (1988). Use rhodamine 123 to investigate alterations in mitochondrial activity in isolated mouse liver mitochondria. Biochem Biophys Res Commun; 151: 568-73.
https://doi.org/10.1016/0006-291X(88)90632-8
 
Perne A, Muellner MK, Steinrueck M, et al. (2009). Cardiac glycosides induce cell death in human cells by inhibiting general protein synthesis. PloS ONE; 4(12): ArticleIDe8292.
https://doi.org/10.1371/journal.pone.0008292
PMid:20016840 PMCid:PMC2788214
 
Prassas I, Diamandis EP. (2008). Novel therapeutic applications of cardiac glycosides. Nat Rev Drug Discov; 7(11): 926-935.
https://doi.org/10.1038/nrd2682
PMid:18948999
 
Saeed MEM, Abdelgadir H, Sugimoto Y, Khalid HE, Efferth T. (2015) Cytotoxicity of 35 medicinal plants from Sudan towards sensitive and multidrug-resistant cancer cells. J. Ethnopharmacol; 174: 644-658.
https://doi.org/10.1016/j.jep.2015.07.005
PMid:26165828
 
Shaw LM. (2005). 'Tumor cell invasion assays', Methods in molecular biology; 97-105.
 
Sofowora A. (1993). Recent trends in research into African medicinal plants. J Ethnopharmacol; 38(2): 197-208.
https://doi.org/10.1016/0378-8741(93)90017-Y
 
Sultan HAS, Abu Elreish BI, Yagi SM. (2010). Anatomical and phytochemical studies of the leaves and roots of Urginea grandiflora Bak. and Pancratium tortuosum Herbert. Ethnobot Leaflets; 14: 826-35.
 
Trease GE, Evans WC. (1989). Pharmacognosy. 11th ed. London: Brailliar Tiridel Can Macmillan Publishers; p. 60-75.
 
Valster A, Tran NL, Nakada M, Berens ME, Chan AY, Symons M. (2005). Cell migration and invasion assays. Methods; 37: 208-215.
https://doi.org/10.1016/j.ymeth.2005.08.001
PMid:16288884
 
Winnicka K, Bielawski K, Bielawska A, Miltyk W. (2010). Dual effects of ouabain, digoxin and proscillaridin A on the regulation of apoptosis in human fibroblasts. Nat Prod Res; 24(3): 274-285.
https://doi.org/10.1080/14786410902991878
PMid:20140806
 
Zhang JH, Xu M. (2000). DNA Fragmentation in apoptosis. J Cell Res; 10: 205-211.
https://doi.org/10.1038/sj.cr.7290049
PMid:11032172

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