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.
Similar content being viewed by others
References
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.
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.
Kerbel RS. Reappraising antiangiogenic therapy for breast cancer. Breast. 2011;20:S56–60.
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.
Siegel R, Naishadham D, Jemal A. Cancer statistics, 2013. CA Cancer J Clin. 2013;63(1):11–30.
Burnett JC, Rossi JJ, Tiemann K. Current progress of siRNA/shRNA therapeutics in clinical trials. Biotechnol J. 2011;6(9):1130–46.
Culver KW, Blaese RM. Gene therapy for cancer. Trends Genet. 1994;10(5):174–8.
Robak T, Wierzbowska A. Current and emerging therapies for acute myeloid leukemia. Clin Ther. 2009;31:2349–70.
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.
Arpinati M, Curti A. Immunotherapy in acute myeloid leukemia. Immunotherapy. 2014;6(1):95–106.
Beatty JD. Immunotherapy of colorectal cancer. Cancer. 1992;70(S3):1425–33.
Saha D, Roman C, Beauchamp RD. New strategies for colorectal cancer prevention and treatment. World J Surg. 2002;26(7):762–6.
Fleshner P, Slater G, Aufses Jr AH. Age and sex distribution of patients with colorectal cancer. Dis Colon Rectum. 1989;32(2):107–11.
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.
Mansoori B, Shotorbani SS, Baradaran B. RNA interference and its role in cancer therapy. Adv Pharm Bull. 2014;4(4):313.
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.
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.
HemaIswarya S, Doble M. Potential synergism of natural products in the treatment of cancer. Phytother Res. 2006;20(4):239–49.
H W KG. Virginia native plants. Virginia: Black Cat Press; 2005.
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.
Ren W, Qiao Z, Wang H, Zhu L, Zhang L. Flavonoids: promising anticancer agents. Med Res Rev. 2003;23(4):519–34.
Sylvester PW, Shah S. Antioxidants in dietary oils: their potential role in breast cancer prevention. Malays J Nutr. 2002;8:1–11.
Baumeister P, Reiter M, Harréus U. Curcumin and other polyphenolic compounds in head and neck cancer chemoprevention. Oxidative Med Cell Longev. 2012;2012:902716.
Chabner BA, Friedman MA. Progress against rare and not-so-rare cancers. N Engl J Med. 1992;326(8):563–5.
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.
Gözüm S, Tezel A, Koc M. Complementary alternative treatments used by patients with cancer in eastern Turkey. Cancer Nurs. 2003;26(3):230–6.
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.
Nahata A, Dixit V. Ameliorative effects of stinging nettle (Urtica dioica) on testosterone‐induced prostatic hyperplasia in rats. Andrologia. 2012;44(s1):396–409.
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.
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.
Horvitz HR. Worms, life, and death (Nobel lecture). Chembiochem. 2003;4(8):697–711.
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.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
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
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12029-016-9819-3