Synergistic Effects of Zygophyllum coccineum and Taurine on SW480 Colon Cancer Cells

Document Type : Research Paper

Authors

Department of Biology, Collage of Science, University of Thi-Qar, Thi-Qar, 64001, Iraq

Abstract

Colorectal cancer is a leading cause of cancer-related deaths worldwide, necessitating the development of novel therapeutic strategies. Since conventional treatments often have limited specificity and significant side effects, this study aimed to investigate the cytotoxic potential of Zygophyllum coccineum C.A.Mey. extracts (aqueous and alcoholic) and taurine, both individually and in combination, against SW480 colon cancer cells. For this purpose, SW480 cells were treated with varying concentrations of aqueous and alcoholic extracts of Z. coccineum, taurine, and combinations thereof. Cell viability was assessed using the MTT assay. The expression of apoptosis-related genes p53 and Bcl2 was quantified using real-time PCR. Results showed that the alcoholic extract of Z. coccineum exhibited greater cytotoxicity towards SW480 cells than the aqueous extract. Taurine alone showed a dose-dependent effect on cell viability. Notably, combining taurine (62.5 µg /mL) with both alcoholic and aqueous extracts significantly enhanced cytotoxicity compared to the extracts alone. Real-time PCR analysis demonstrated that treatment of SW480 colon cancer cells with Z. coccineum extracts (both aqueous and alcoholic) and taurine led to a significant upregulation of the pro-apoptotic gene P53, along with either an increase or modulation of the anti-apoptotic gene Bcl2. The highest induction of P53 expression was observed with the combination of alcoholic extract and taurine (14.75-fold), while the lowest Bcl2 expression was also recorded in this group (1.07-fold). This pattern indicates a synergistic effect in enhancing apoptotic pathways and controlling cell proliferation, suggesting potential anti-cancer efficacy of these treatments. In conclusion, Z. coccineum extracts, particularly when combined with taurine, demonstrate significant cytotoxic activity against SW480 cells. The synergistic effect of the extract and taurine suggests a potential therapeutic strategy for colorectal cancer by promoting apoptosis.

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Main Subjects


  1. WHO, World Health Organization. Cancer. https://www.who.int/news-room/fact-sheets/detail/cancer
  2. Ross D.W. Introduction to oncogenes and molecular cancer medicine. Springer New York, NY. 2012;168.
  3. Kooti W., Servatyari K., Behzadifar M., Asadi-Samani M., Sadeghi F., Nouri B., Zare Marzouni H. Effective medicinal plant in cancer treatment, part 2: review study. Evidence-Based Complementary and Alternative Medicine. 2017;22(4):982-995.
  4. Ross I.A. Medicinal plants of the world, volume 3: Chemical constituents, traditional and modern medicinal uses. Springer Science & Business Media. 2007.
  5. Naji W.A., Enaya S.H., Malih H.R. Studying the effect of flavonoids extracted from Haloxylon salicornium and Z. coccinium plants on burn healing in diabetic white rabbits. The Egyptian Journal of Hospital Medicine. 2023;90(1):1542-1557.
  6. Desai A.G., Qazi G.N., Ganju R.K., El-Tamer M., Singh J., Saxena A.K., Bedi Y.S., Taneja S.C., Bhat H.K. Medicinal plants and cancer chemoprevention. Current Drug Metabolism. 2008;9(7):581-591.
  7. Abdel-Mogib M., Salih L.M., Allah Hesham M. A comparative study on phytochemical constituents of Zygophyllum coccineum L. in coastal and inland desert of Egypt. International Journal on Engineering Applications. 2015;4(6):1-4.
  8. Elgamal M.H., Shaker K.H., Pöllmann K., Seifert K. Triterpenoid saponins from Zygophyllum species. Phytochemistry. 1995;40(4):1233-1236.
  9. Gibbons S., Oriowo M.A. Antihypertensive effect of an aqueous extract of Zygophyllum coccineum L. in rats. Phytotherapy Research. 2001;15(5):452-455.
  10. Elbadry M.A., Elaasser M.M., Elshiekh H.H., Sheriff M.M. Evaluation of antimicrobial, cytotoxic and larvicidal activity of Zygophyllum coccineum North Sinai, Egypt. Medicinal and Aromatic Plants. 2015;4(5):214.
  11. Abd El Raheim M., Alam A., Nour Y.S., Radwan A.M. Evaluation of antimicrobial and antioxidant activities of Matricaria recutita, Ricinus communis and Zygophyllum coccineum Extracts. Bulletin of Environment, Pharmacology and Life Sciences. 2016;5:30-33.
  12. El-Shora H.M., El-Amier Y.A., Awad M.H. Antioxidant activity of leaf extracts from Zygophyllum coccineum L. collected from desert and coastal habitats of Egypt. International Journal of Current Microbiology and Applied Sciences. 2016;5(4):635-641.
  13. Coughlin S.S., Ekwueme D.U. Breast cancer as a global health concern. Cancer Epidemiology. 2009;33(5):315-318.
  14. Prestinaci F., Pezzotti P., Pantosti A. Antimicrobial resistance: A global multifaceted phenomenon. Pathogens and Global Health. 2015;109(7):309-318.
  15. Wang L., Zhao N., Zhang F., Yue W., Liang M. Effect of taurine on leucocyte function. European Journal of Pharmacology. 2009;616(1-3):275-280.
  16. Ripps H., Shen W. Review: taurine: A "very essential" amino acid. Molecular Vision. 2012;18:2673-2686.
  17. Militante J.D., Lombardini J.B. Taurine: evidence of physiological function in the retina. Nutritional Neuroscience. 2002;5(2):75-90.
  18. Yu J.S., Kim A.K. Effect of combination of taurine and azelaic acid on antimelanogenesis in murine melanoma cells. J. Biomed. Sci. 2010;17:1-5.
  19. Tu S., Zhang X., Luo D., Liu Z., Yang X., Wan H., Yu L., Li H., Wan F. Effect of taurine on the proliferation and apoptosis of human hepatocellular carcinoma HepG2 cells. Experimental and Therapeutic Medicine. 2015;10(1):193-200.
  20. Song X., Yuan B., Zhao S., Zhao D. Effect of taurine on the proliferation, apoptosis and MST1/Hippo signaling in prostate cancer cells. Translational Cancer Research. 2022;11(6):1705.
  21. Hou X., Hu J., Zhao X., Wei Q., Zhao R., Li M., Li Q. Taurine attenuates the hypotaurine-induced progression of CRC via ERK/RSK signaling. Frontiers in Cell and Developmental Biology. 2021;9:631163.
  22. Zhang X., Tu S., Wang Y., Xu B., Wan F. Mechanism of taurine-induced apoptosis in human colon cancer cells. Acta Biochim. Biophys. Sin. 2014;46(4):261-272.
  23. Moustafa S.M., Menshawi B.M., Wassel G.M., Mahmoud K., Marwa M.M. Screening of some plants in Egypt for their cytotoxicity against four human cancer cell lines. Int. J. Pharmtech Res. 2014;6(3):1074-1084.
  24. El-Shora H.M., El-Amier Y.A., Awad M.H. Antimicrobial activity and allelopathic potential of Zygophyllum coccineum L. on Chenopodium album L. Br. J. Appl. Sci. Technol. 2016;15(5).
  25. Rebouças E.D., Costa J.J., Passos M.J., Passos J.R., Hurk R.V., Silva J.R. Real time PCR and importance of housekeepings genes for normalization and quantification of mRNA expression in different tissues. Brazilian Archives of Biology and Technology. 2013;56:143-154.
  26. Livak K.J., Schmittgen T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2− ΔΔCT method. Methods. 2001;25(4):402-408.
  27. Hewish M., Lord C.J., Martin S.A., Cunningham D., Ashworth A. Mismatch repair deficient colorectal cancer in the era of personalized treatment. Nature Reviews Clinical Oncology. 2010;7(4):197-208.
  28. Ragnhammar P., Brorsson B., Nygren P., Glimelius B. A prospective study of the use of chemotherapy in Sweden and assessment of the use in relation to scientific evidence. Acta Oncologica. 2001;40(2-3):391-411.
  29. Al-Muswie R.T., Enayah S.H., Ghaleb R.A. Synergistic effects of Cassia fistula extract combination with cisplatin on the regulation of microRNA-145 and gene expression in colon cancer cell line SW480. Medical Journal of Babylon. 2023;20(4):670-680.
  30. Misale S., Yaeger R., Hobor S., Scala E., Janakiraman M., Liska D., Valtorta E., Schiavo R., Buscarino M., Siravegna G., Bencardino K. Emergence of KRAS mutations and acquired resistance to anti-EGFR therapy in colorectal cancer. Nature. 2012;486(7404):532-536.
  31. Hugen N., Brown G., Glynne-Jones R., de Wilt J.H., Nagtegaal I.D. Advances in the care of patients with mucinous colorectal cancer. Nature Reviews Clinical Oncology. 2016;13(6):361-369.
  32. Sui Q., Zhang J., Chen M., Tong J., Wang R., Wei Y. Distribution of antibiotic resistance genes (ARGs) in anaerobic digestion and land application of swine wastewater. Environmental Pollution. 2016;213:751-759.
  33. Latif A., Amer H.M., Hamad M.E., Alarifi S.A., Almajhdi F.N. Medicinal plants from Saudi Arabia and Indonesia: In vitro cytotoxicity evaluation on Vero and Hep-2 cells. Journal of Medicinal Plants Research. 2014;8(34):1065-1073.
  34. Roy A., Ahuja S., Bharadvaja N. A review on medicinal plants against cancer. Journal of Plant Sciences and Agricultural Research. 2017;2(1):8.
  35. El-Afify S.M., El-Metwaly M.A., Abbas M.A., El-Amier Y.A. In vitro assessment of antioxidant and cytotoxic activities of Zygophyllum coccineum L. methanolic extract. Egyptian Journal of Chemistry. 2024;67(2):393-401.
  36. Mohammed H.A., Khan R.A., Abdel-Hafez A.A., Abdel-Aziz M., Ahmed E., Enany S., Mahgoub S., Al-Rugaie O., Alsharidah M., Aly M.S., Mehany A.B. Phytochemical profiling, in vitro and in silico anti-microbial and anti-cancer activity evaluations and Staph GyraseB and h-TOP-IIβ receptor-docking studies of major constituents of Zygophyllum coccineum L. Aqueous-ethanolic extract and its subsequent fractions: An approach to validate traditional phytomedicinal knowledge. Molecules. 2021;26(3):577.
  37. Jiang M., Milner J. Bcl-2 constitutively suppresses p53-dependent apoptosis in colorectal cancer cells. Genes & Development. 2003;17(7):832-837.
  38. El Agouza I.M., Eissa S.S., El Houseini M.M., El-Nashar D.E., Abd El Hameed O.M. Taurine: A novel tumor marker for enhanced detection of breast cancer among female patients. Angiogenesis. 2011;14:321-330.
  39. Srivastava S., Roy R., Singh S., Kumar P., Dalela D., Sankhwar S.N., Goel A., Sonkar A.A. Taurine–a possible fingerprint biomarker in non-muscle invasive bladder cancer: A pilot study by 1H NMR spectroscopy. Cancer Biomarkers. 2009;6(1):11-20.
  40. Tu S., Zhang X.L., Wan H.F., Xia Y.Q., Liu Z.Q., Yang X.H., Wan F.S. Effect of taurine on cell proliferation and apoptosis human lung cancer A549 cells. Oncology Letters. 2018;15(4):5473-5480.
  41. Reddy B.S., Rao C.V., Rivenson A., Kelloff G. Chemoprevention of colon carcinogenesis by organosulfur compounds. Cancer Research. 1993;53(15):3493-3498.
  42. Hernández-Benítez R., Ramos-Mandujano G., Pasantes-Morales H. Taurine stimulates proliferation and promotes neurogenesis of mouse adult cultured neural stem/progenitor cells. Stem Cell Research. 2012;9(1):24-34.
  43. Mori H., Ninomiya K., Kino‐oka M., Shofuda T., Islam M.O., Yamasaki M., Okano H., Taya M., Kanemura Y. Effect of neurosphere size on the growth rate of human neural stem/progenitor cells. Journal of Neuroscience Research. 2006;84(8):1682-16891.
  44. Jeong J.E., Kim T.Y., Park H.J., Lee K.H., Lee K.H., Choi E.J., Kim J.K., Chung H.L., Seo E.S., Kim W.T. Taurine exerts neuroprotective effects via anti-apoptosis in hypoxic-ischemic brain injury in neonatal rats. Clinical and Experimental Pediatrics. 2009;52(12):1337-1347.
  45. Jeon S.H., Lee M.Y., Kim S.J., Joe S.G., Kim G.B., Kim I.S., Kim N.S., Hong C.U., Kim S.Z., Kim J.S., Kang H.S. Taurine increases cell proliferation and generates an increase in [Mg2+] i accompanied by ERK 1/2 activation in human osteoblast cells. FEBS Letters. 2007;581(30):5929-5934.
  46. Hao Q., Wang L., Zhang M., Wang Z., Li M., Gao X. Taurine stimulates protein synthesis and proliferation of C2C12 myoblast cells through the PI3K-ARID4B-mTOR pathway. British Journal of Nutrition. 2022;128(10):1875-1886.
  47. Zhuo L., Liao M., Zheng L., He M., Huang Q., Wei L., Huang R., Zhang S., Lin X. Combination therapy with taurine, epigallocatechin gallate and genistein for protection against hepatic fibrosis induced by alcohol in rats. Biological and Pharmaceutical Bulletin. 2012;35(10):1802-1810.