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Validation of the antiproliferative effects of Euphorbia tirucalli extracts in breast cancer cell lines

  • Molecular Cell Biology
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Abstract

Medicinal plant extracts have recently attracted attention of modern medical science research due to their non-lethal activity. Currently, up to 50% of the world drugs including chemotherapeutic drugs such as taxol and camptothecin are derived from natural products. Euphorbia tirucalli has a long history of usage as traditional medicine in Africa and has been widely used in the treatment of different cancers. In this study, we explore the medical properties of E. tirucalli extracts in breast cancer development. To achieve this, stems of E. tirucalli were dried, crushed and extracted with butanol, hexane or methanol (based on 1 g of dry substance in 10 mL of a solvent). The dried extracts were re-dissolved in DMSO and investigated. Composition of each extract was analyzed using liquid chromatography-mass spectroscopy (LC-MS). Extracts were found to contain different types of secondary metabolites mainly terpenes and flavonoids. Breast cancer cell lines (MCF-7 and MDA-MB 231) were treated with various concentrations of the extracts for up to 48 h. Cell viability, cell cycle, apoptosis and gene expression were analysed. In cells, extracts were found to inhibit cell proliferation in a concentration and cell type dependent manner. Analysis of the cause of antiproliferation revealed that most cells were arrested at the G0/G1 phase by p21 overexpression. In general, most pro-apoptotic genes like Bax and caspase-8 were significantly up-regulated in cells treated with plant extracts. These results suggest that the extracts might induce cell cycle arrest at G0/G1 with p21 attributing to this molecular mechanism.

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References

  1. Singh Y.N. 1986. Traditional medicine in Fiji: Some herbal folk cures used by Fiji Indians. J. Ethnopharmacol. 15, 57–88.

    Article  CAS  PubMed  Google Scholar 

  2. Igoli J.O., Ogaji O.G., Tor-Anyiin T.A., Igoli N.P. 2005. Traditional medicine practise amongst the Igede people of Nigeria. Part II. Afr. J. Tradit. Complement. Altern. Med. 2, 134–152.

    Google Scholar 

  3. Rizk A.F.M. 1987. The chemical constituents and economic plants of the Euphorbiaceae. Bot. J. Linn. Soc. 94, 293–326.

    Article  Google Scholar 

  4. Sayed M.D. 1980. Traditional medicine in healthcare. J. Ethnopharmacol. 2, 19–22.

    Article  CAS  PubMed  Google Scholar 

  5. van Wyk B.E., De Wet H., van Heerden F.R. 2008. An ethnobotanical survey of medicinal plants in the southeastern Karoo, South Africa. S. Afr. J. Bot. 74, 696–704.

    Article  Google Scholar 

  6. Gurib-Fakim A. 2006. Medicinal plants: Traditions of yesterday and drugs of tomorrow. Mol. Aspects Med. 27, 1–93.

    Article  CAS  PubMed  Google Scholar 

  7. Singh S.B., Barrett J.F. 2006. Empirical antibacterial drug discovery: Foundation in natural products. Biochem. Pharmacol. 71, 1006–1015.

    Article  CAS  PubMed  Google Scholar 

  8. Itokawa H., Morris-Natschke S.L., Akiyam, T., Lee K.H. 2008. Plant-derived natural product research aimed at new drug discovery. J. Nat. Med. 62, 263–280.

    Article  CAS  PubMed  Google Scholar 

  9. Pezzuto J.M., 1997. Plant-derived anticancer agents. Biochem. Pharmacol. 53, 121–133.

    Article  CAS  PubMed  Google Scholar 

  10. Siegel R., Ward E., Brawley O., Jemal A. 2011. Cancer Statistics, 2011. The impact of eliminating socioeconomic and racial disparities on premature cancer deaths. CA: Cancer J. Clin. 61, 212–236.

    Google Scholar 

  11. Reddivari L., Vanamala J., Safe S.H., Miller J.C., 2010. The bioactive compounds alpha-chaconine and gallic acid in potato extracts decrease survival and induce apoptosis in LNCaP and PC3 prostate cancer cells. Nutr. Cancer. 62, 601–610.

    Article  CAS  PubMed  Google Scholar 

  12. Idibie C.A., Davids H., Iyuke S.E. 2007. Cytotoxicity of purified cassava linamarin to a selected cancer cell lines. Bioprocess Biosyst. Eng. 30, 261–269.

    Article  CAS  PubMed  Google Scholar 

  13. Kim M.E., Ha T.K., Yoon J.H., Lee J.S. 2014. Myricetin induces cell death of human colon cancer cells via BAX/BCL2-dependent pathway. Anticancer Res. 34, 701–706.

    CAS  PubMed  Google Scholar 

  14. Aboul-Fadl T., Radwan A.A., Attia M.I., Al-Dhfyan A., Abdel-Aziz H.A. 2012. Schiff bases of indoline-2,3- dione (isatin) with potential antiproliferative activity. Chem. Cent. J. 6, 49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Emirdag-Öztürka S., Karayildirima T., Çapci-Karagözb A., Alankus-Çaliskana O., Özmenc A., Poyrazoglu-Çobanc E. 2014. Synthesis, antimicrobial and cytotoxic activities, and structure–activity relationships of gypsogenin derivatives against human cancer cells. Eur. J. Med. Chem. 82, 565–573.

    Article  Google Scholar 

  16. Devarajan E., Sahin A.A., Chen J.S., Krishnamurthy R.R., Aggarwal N., Brun A., Sapino A., Zhang F., Sharma D., Yang X.H., Tora A.D., Mehta K. 2002. Down-regulation of caspase 3 in breast cancer: a possible mechanism for chemoresistance. Oncogene. 21, 8843–8851.

    Article  CAS  PubMed  Google Scholar 

  17. Vorobiof D.A., Sitas F., Vorobiof G. 2001. Breast cancer incidence in South Africa. J. Clin. Oncol. 19, 125–127.

    Google Scholar 

  18. Gehl J., Boesgaard M., Paaske T., Vittrup Jensen B., Dombernowsky P. 1996. Combined doxorubicin and paclitaxel in advanced breast cancer: Effective and cardiotoxic. Ann. Oncol. 7, 687–693.

    Article  CAS  PubMed  Google Scholar 

  19. Aljabarin K.L., Farraj M., Jabarin B., Feng Z.J. 2014. Antimicrobial susceptibility of Euphorbia tirucalli extracts and the effect of latex on growth and viability of mouse breast cancer cells EMT-6. IOSR J. Dental Med. Sci. 13, 59–63.

    Article  Google Scholar 

  20. Betancur-Galvis L.A., Morales G.E., Forero J.E., Roldan J. 2002. Cytotoxic and antiviral activities of Colombian medicinal plant extracts of the Euphorbia genus. Mem. Inst. Oswaldo Cruz. 97, 541–546.

    Article  CAS  PubMed  Google Scholar 

  21. Miglietta A., Gabriel L., Appendino G., Bocca C. 2002. Biological properties of jatrophane polyesters, new microtubule-interacting agents. Cancer Chemother. Pharm. 51, 67–74.

    Article  Google Scholar 

  22. Spiridonov N.A., Konovalov D.A., Arkhipov V.V. 2005. Cytotoxicity of some Russian ethnomedicinal plants and plant compounds. Phytother. Res. 19, 428–432.

    Article  CAS  PubMed  Google Scholar 

  23. Thafeni M., Sayed Y., Motadi L. 2012. Euphorbia mauritanica and Kedrostis hirtella extracts induces cell death in lung cancer cells. J. Mol. Biol. 39, 10785–10794.

    CAS  Google Scholar 

  24. Amirghofran Z., Bahmani M., Azadmehr A., Javidnia K. 2006. Induction of apoptosis in leukemia cell lines by Linum persicum and Euphorbia cheiradenia. J. Cancer. Res. Clin. Oncol. 132, 427–432.

    Article  PubMed  Google Scholar 

  25. Ke N., Wang X., Xu X., Abassi Y.A. 2010. The xCELLigence system for real-time and label-free monitoring of cell viability. Methods Mol. Biol. 740, 33–43.

    Article  Google Scholar 

  26. Moniri M.R., Young A., Reinheimer K., Rayat J., Dai L.J., Warnock G.L. 2015. Dynamic assessment of cell viability, proliferation and migration using real time cell analyzer system (RTCA). Cytotechnology. 67, 379–386.

    Article  Google Scholar 

  27. Meindl C., Absenger M., Roblegg E., Fröhlich E. 2013. Suitability of cell-based label-free detection for cytotoxicity screening of carbon nanotubes. Biomed. Res. Int. 2013, 564804.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Moela P., Choene M.S., Motadi L.R. 2014. Silencing RBBP6 (Retinoblastoma Binding Protein 6) sensitises breast cancer cells MCF7 to staurosporine and camptothecin- induced cell death. Immunobiology. 219, 593–601.

    Article  CAS  PubMed  Google Scholar 

  29. Liu X., Li Q., Dowdell K., Fischer E.R., Cohen J.I. 2012. Varicella-zoster virus ORF12 protein triggers phosphorylation of ERK1/2 and inhibits apoptosis. J. Virol. 86, 3143–3151.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Szarc vel Szic K., Op De Beeck K., Ratman D., Wouters A., Beck I.M., Declerck K., Heyninck K., Fransen E., Bracke M., De Bosscher K., Lardon F., van Camp G., Vanden Berghe W. 2014. Pharmacological levels of withaferin A (Withania somnifera) trigger clinically relevant anticancer effects specific to triple negative breast cancer cells. PLoS ONE. 9, e87850.

    Article  Google Scholar 

  31. Looi C.Y., Arya A., Cheah F.K., Muharram B., Leong K.H., Mohamad K., Wong W.F., Rai N., Mustafa M.R. 2013. Induction of apoptosis in human breast cancer cells via caspase pathway by vernodalin isolated from Centratherum anthelminticum (L.) seeds. PLoS ONE. 8, e56643.

    Article  Google Scholar 

  32. Fulda S., Debatin K.M. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene. 25, 4798–4811.

    Article  CAS  PubMed  Google Scholar 

  33. Fulda S. 2009. Tumor resistance to apoptosis. Int. J. Cancer. 124, 511–515.

    Article  CAS  PubMed  Google Scholar 

  34. Shapiro G.I., Harper J.W. 1999. Anticancer drug targets: cell cycle and checkpoint control. J. Clin. Invest. 104, 12.

    Article  Google Scholar 

  35. Jansen B., Wacheck V., Heere-Ress E., Schlagbauer- Wadl H., Hoeller C., Lucas T., Hoermann M., Hollenstein U., Wolff K., Pehamberger H. 2000. Chemosensitisation of malignant melanoma by BCL2 antisense therapy. Lancet. 356, 1728–1733.

    Article  CAS  PubMed  Google Scholar 

  36. Kastan M.B., Onyekwere O., Sidransky D., Vogelstein B., Craig R. 1991. Participation of p53 protein in the cellular response to DNA damage. Cancer Res. 51, 6304–6311.

    CAS  PubMed  Google Scholar 

  37. Agarwal M.L., Agarwal A., Taylor W.R., Stark G.R. 1995. p53 controls both the G2/M and the G1 cell cycle checkpoints and mediates reversible growth arrest in human. J. Cell Biol. 92, 8493–8497.

    CAS  Google Scholar 

  38. Choene M.S., Motadi L.R. 2012. Anti-proliferative effects of methanolic extract of Kedrostis foetidissima in breast cancer cell lines. Mol. Biol. 1, 107. doi 10.4172/2168-9547.1000107

    Article  Google Scholar 

  39. Mahassni S.H., Al-Reemi R.M. 2012. Apoptosis and necrosis of human breast cancer cells by an aqueous extract of garden cress (Lepidium sativum) seeds. Saudi J. Biol. Sci. 20, 131–139.

    Article  Google Scholar 

  40. Hsieh Y., Chang C., Wan C., Chen C, Yi-Han Chiu, Y., Leu Y., Peng K. 2013. Euphorbia formosana root extract induces apoptosis by caspase-dependent cell death via Fas and mitochondrial pathway in THP-1 human leukemic cells. Molecules. 18, 1949–1962.

    Article  CAS  PubMed  Google Scholar 

  41. Ujiki M.B., Ding X.Z., Salabat M.R., Bentrem D.J., Golkar L., Milam B., Talamonti M.S., Bell R.H., Iwamura T., Adrian T.E. 2006. Apigenin inhibits pancreatic cancer cell proliferation through G2/M cell cycle arrest. Mol. Cancer. 5, 76.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Krifa M., Alhosin M., Muller C.D., Gies J., Chekir-Ghedira L., Ghedira K., Mély Y., Bronner C., Mousli M. 2013. Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16INK4A re-expression related to UHRF1 and DNMT1 down-regulation. J. Exp. Clin. Cancer Res. 32, 30.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Williams G.T., Smith C.A. 1993. Molecular regulation of apoptosis: genetic controls on cell death. Cell. 74, 777–779.

    Article  CAS  PubMed  Google Scholar 

  44. Raisova M., Hossini A.M., Eberle J., Riebeling C., Wieder T., Sturm I., Daniel P.T., Orfanos C.E., Geilen C.C. 2001. The Bax/Bcl-2 ratio determines the susceptibility of human melanoma cells to CD95/Fas-mediated apoptosis. J. Invest. Dermatol. 117, 333–340.

    Article  CAS  PubMed  Google Scholar 

  45. Alshatwi A.A., Hasan T.N., Shafi G., Syed N.A., Al- Assaf A.H., Alamri M.S., Al-Khalifa A.S. 2012. Validation of the antiproliferative effects of organic extracts from the green husk of Juglans regia L. on PC-3 human prostate cancer cells by assessment of apoptosis-related genes. Evid. Based Complement. Alternat. Med. 2012, 103026.

    PubMed  Google Scholar 

  46. Huppertz B., Frank H.-G., Kaufmann P. 1999. The apoptosis cascade: Morphological and immunohistochemical methods for its visualization. Anat. Embryol. 200, 1–18.

    Article  CAS  PubMed  Google Scholar 

  47. Brauns S.C., Dealtry G., Milne P., Naude R., Van De Venter M. 2005. Caspase-3 activation and induction of PARP cleavage by cyclic dipeptide cyclo(Phe-Pro) in HT-29 cells. Anticancer Res. 25, 4197–4202.

    CAS  PubMed  Google Scholar 

  48. Yaacob N.S., Hamzah N., Kamal N.N.N.M., Abidin S.A.Z., Lai C.S., Navaratnam V., Norazmi M.N. 2010. Anticancer activity of a sub-fraction of dichloromethane extract of Strobilanthes crispus on human breast and prostate cancer cells in vitro. BMC Complement. Altern. Med. 10, 42.

    Article  PubMed  PubMed Central  Google Scholar 

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  1. Department of Biochemistry, North-West University (Mafikeng Campus), Private Bag X1290, Potchefstroom, South Africa, 2520

    M. Choene & L. Motadi

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  1. M. Choene
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  2. L. Motadi
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Correspondence to L. Motadi.

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Published in Russian in Molekulyarnaya Biologiya, 2016, Vol. 50, No. 1, pp. 115–128.

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Choene, M., Motadi, L. Validation of the antiproliferative effects of Euphorbia tirucalli extracts in breast cancer cell lines. Mol Biol 50, 98–110 (2016). https://doi.org/10.1134/S0026893316010040

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