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*
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
U. grandiflora could be a new source of chemotherapeutic for breast cancer.
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
|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.
|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.
|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.
|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.
|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.
|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.
|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.
|Cragg GM, Newmann DJ. (2005). Plants as source of anticancer agents. J. Ethnopharmacol; 100: 72-79.
|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.
|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.
|Eguchi K. (2001). Apoptosis in autoimmune diseases. Intern Med; 40: 275-284.
|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.
|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.
|Franken NP, Rodermond H, Stap J, Haveman J, Bree C. Clonogenic assay of cells in vitro. Nat Protoc 2006; 1(5): 2315-2319.
|Foo J, Michor F. Evolution of acquired resistance to anti-cancer therapy. (2014). J Theor Biol; 355: 10-20
|Harborne Jb. (1984). Phytochemical Methods. 2nd edition, Springer; p 37-99.
|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.
|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.
|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.
|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.
|Mosmann T. (1983). Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunological Methods; 65: 55-63.
|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.
|Newman RA, Yang P, Pawlus AD, Block KI. (2008). Cardiac glycosides as novel cancer therapeutic agents. Mol Interv; 8(1): 36-49.
|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.
|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.
|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.
|Prassas I, Diamandis EP. (2008). Novel therapeutic applications of cardiac glycosides. Nat Rev Drug Discov; 7(11): 926-935.
|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.
|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.
|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.
|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.
|Zhang JH, Xu M. (2000). DNA Fragmentation in apoptosis. J Cell Res; 10: 205-211.