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The Herbal Medicine Utrica Dioica Inhibits Proliferation of Colorectal Cancer Cell Line by Inducing Apoptosis and Arrest at the G2/M Phase

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Abstract

Background

One of the major causes of cancer death internationally and the third most prevalent cancer in the world has been diagnosed with colorectal cancer. Although current routine treatments of cancer have been successful in some extent, mortality caused by adverse effects of these strategies is still raising. Medicinal plants are potential sources of anticancer compounds and can be exploited as a powerful complementary tool. This study aimed to investigate the cytotoxic effects of nettle extract on mouse colorectal cancer cells, HCT.

Materials and Methods

In the present study, to evaluate the cytotoxicity of nettle extract, MTT assay and trypan blue were performed. Subsequently, DNA fragmentation and TUNEL test was carried out for determination of apoptosis. Real-time PCR test was used to quantify the expression of Caspase-3, Caspase-9, and Bcl-2 which is involved in apoptosis regulation. Finally, cell cycle analysis was conducted by using flow cytometry.

Results

The results of MTT assay showed that the dichloromethane extract of U. dioica extract significantly destroyed cancer cells HCT-116. DNA fragmentation and TUNEL test demonstrated that Utrica extract elicited apoptotic response in the cancer cells. The messenger RNA (mRNA) expression levels of Caspase-3 and Caspase-9 markedly increased, while the Bcl-2 gene was conversely downregulated. Findings of flow cytometry confirmed that cell cycle arrest has occurred at the G2 phase.

Conclusion

Taken together, our experiment showed that subjecting HCT-116 cells to dichloromethane extract of nettle (U. dioica), increases turnover of these cells. Thus, it may be a useful agent in the treatment of colorectal cancer.

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References

  1. Medina-Ramirez CM, Goswami S, Smirnova T, Bamira D, Benson B, Ferrick N, et al. Apoptosis inhibitor ARC promotes breast tumorigenesis, metastasis, and chemoresistance. Cancer Res. 2011;71(24):7705–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bhalla KN, Rao R, Sharma P, Das Gupta S, Chauhan L, Stecklein S, et al. Treatment with histone deacetylase inhibitors creates ‘BRCAness’ and sensitizes human triple negative breast cancer cells to PARP inhibitors and cisplatin. Cancer Res. 2012;72(24 Supplement):S3–7.

    Article  Google Scholar 

  3. Kerbel RS. Reappraising antiangiogenic therapy for breast cancer. Breast. 2011;20:S56–60.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Zhang Y, Peng L, Mumper RJ, Huang L. Combinational delivery of c-myc siRNA and nucleoside analogs in a single, synthetic nanocarrier for targeted cancer therapy. Biomaterials. 2013;34(33):8459–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.

    Article  PubMed  Google Scholar 

  6. Burnett JC, Rossi JJ, Tiemann K. Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol J. 2011;6(9):1130–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Culver KW, Blaese RM. Gene therapy for cancer. Trends Genet. 1994;10(5):174–8.

    Article  CAS  PubMed  Google Scholar 

  8. Robak T, Wierzbowska A. Current and emerging therapies for acute myeloid leukemia. Clin Ther. 2009;31:2349–70.

    Article  CAS  PubMed  Google Scholar 

  9. Kupsa T, Milos Horacek J, Jebavy L. The role of cytokines in acute myeloid leukemia: a systematic review. Biomed Pap. 2012;156(4):291–301.

    CAS  Google Scholar 

  10. Arpinati M, Curti A. Immunotherapy in acute myeloid leukemia. Immunotherapy. 2014;6(1):95–106.

    Article  CAS  PubMed  Google Scholar 

  11. Beatty JD. Immunotherapy of colorectal cancer. Cancer. 1992;70(S3):1425–33.

    Article  CAS  PubMed  Google Scholar 

  12. Saha D, Roman C, Beauchamp RD. New strategies for colorectal cancer prevention and treatment. World J Surg. 2002;26(7):762–6.

    Article  PubMed  Google Scholar 

  13. Fleshner P, Slater G, Aufses Jr AH. Age and sex distribution of patients with colorectal cancer. Dis Colon Rectum. 1989;32(2):107–11.

    Article  CAS  PubMed  Google Scholar 

  14. Chattar-Cora D, Onime GD, Valentine IS, Cudjoe E, Rivera L. Colorectal cancer in a multi-ethnic urban group: its anatomical and age profile. Int Surg. 1999;85(2):137–42.

    Google Scholar 

  15. Mansoori B, Shotorbani SS, Baradaran B. RNA interference and its role in cancer therapy. Adv Pharm Bull. 2014;4(4):313.

    PubMed  PubMed Central  Google Scholar 

  16. Mansoori B, Mohammadi A, Shir Jang S, Baradaran B. Mechanisms of immune system activation in mammalians by small interfering RNA (siRNA). Artif Cells Nanomed Biotechnol. 2015;26:1–8.

    Article  Google Scholar 

  17. Gritsko T, Williams A, Turkson J, Kaneko S, Bowman T, Huang M, et al. Persistent activation of stat3 signaling induces survivin gene expression and confers resistance to apoptosis in human breast cancer cells. Clin Cancer Res. 2006;12(1):11–9.

    Article  CAS  PubMed  Google Scholar 

  18. HemaIswarya S, Doble M. Potential synergism of natural products in the treatment of cancer. Phytother Res. 2006;20(4):239–49.

    Article  CAS  PubMed  Google Scholar 

  19. H W KG. Virginia native plants. Virginia: Black Cat Press; 2005.

  20. Mohammadi A, Mansoori B, Goldar S, Shanehbandi D, Khaze V, Mohammadnejad L, et al. Effects of Urtica dioica dichloromethane extract on cell apoptosis and related gene expression in human breast cancer cell line (MDA-MB-468). Cell Mol Biol. 2016;62(2):62. Noisy-le-Grand, France.

    CAS  PubMed  Google Scholar 

  21. Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev. 2003;23(4):519–34.

    Article  CAS  PubMed  Google Scholar 

  22. Sylvester PW, Shah S. Antioxidants in dietary oils: their potential role in breast cancer prevention. Malays J Nutr. 2002;8:1–11.

    PubMed  Google Scholar 

  23. Baumeister P, Reiter M, Harréus U. Curcumin and other polyphenolic compounds in head and neck cancer chemoprevention. Oxidative Med Cell Longev. 2012;2012:902716.

    Article  Google Scholar 

  24. Chabner BA, Friedman MA. Progress against rare and not-so-rare cancers. N Engl J Med. 1992;326(8):563–5.

    Article  CAS  PubMed  Google Scholar 

  25. Ait-Mohamed O, Battisti V, Joliot V, Fritsch L, Pontis J, Medjkane S, et al. Acetonic extract of buxus sempervirens induces cell cycle arrest, apoptosis and autophagy in breast cancer cells. PLoS ONE. 2011;6(9):e24537.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gözüm S, Tezel A, Koc M. Complementary alternative treatments used by patients with cancer in eastern Turkey. Cancer Nurs. 2003;26(3):230–6.

    Article  PubMed  Google Scholar 

  27. Konrad L, Müller H-H, Lenz C, Laubinger H, Aumüller G, Lichius JJ. Antiproliferative effect on human prostate cancer cells by a stinging nettle root (Urtica dioica) extract. Planta Med. 2000;66(1):44–7.

    Article  CAS  PubMed  Google Scholar 

  28. Nahata A, Dixit V. Ameliorative effects of stinging nettle (Urtica dioica) on testosterone‐induced prostatic hyperplasia in rats. Andrologia. 2012;44(s1):396–409.

    Article  PubMed  Google Scholar 

  29. Harput US, Saracoglu I, Ogihara Y. Stimulation of lymphocyte proliferation and inhibition of nitric oxide production by aqueous Urtica dioica extract. Phytother Res. 2005;19(4):346–8.

    Article  PubMed  Google Scholar 

  30. Yener Z, Celik I, Ilhan F, Bal R. Effects of Urtica dioica L. seed on lipid peroxidation, antioxidants and liver pathology in aflatoxin-induced tissue injury in rats. Food Chem Toxicol. 2009;47(2):418–24.

    Article  CAS  PubMed  Google Scholar 

  31. Horvitz HR. Worms, life, and death (Nobel lecture). Chembiochem. 2003;4(8):697–711.

    Article  CAS  PubMed  Google Scholar 

  32. Kao C, Hsieh C, Chen C, Liu C. The pharmacological effects of natural products and herbs in benign prostatic hyperplasia. Austin J Nutr Food Sci. 2014;2(10):1054.

    Google Scholar 

Download references

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Correspondence to Behzad Baradaran.

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Mohammadi, A., Mansoori, B., Aghapour, M. et al. The Herbal Medicine Utrica Dioica Inhibits Proliferation of Colorectal Cancer Cell Line by Inducing Apoptosis and Arrest at the G2/M Phase. J Gastrointest Canc 47, 187–195 (2016). https://doi.org/10.1007/s12029-016-9819-3

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  • DOI: https://doi.org/10.1007/s12029-016-9819-3

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