Evaluation of Cytotoxicity Activity and NM23 Gene Expression in T47D Breast Cancer Cell Line Treated with Glycyrrhiza glabra Extract

Document Type : Research Article

Authors

1 Department of Biology, Central Tehran Branch, Islamic Azad University, Tehran, Iran

2 Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran

Abstract

Glycyrrhiza is a genus of about 20 accepted species in the legume family (Fabaceae), with a distribution in Asia, Australia, Europe, and the Americas. Recently, about 30 species from the genus Glycyrrhiza have been found and used in traditional medicine for treating cancer. Different studies confirmed that down regulation of Non-metastatic protein (NM23), a metastasis suppressor gene is related to high metastatic potential. The aim of this study was to investigate the effect of Glycyrrhiza glabra extract on the expression of NM23 gene and against breast cancer (T47D) cell line. In this study, T47D cancer and MRC-5 normal cell lines were treated with different concentrations (0.1, 0.2, 0.5, 1, 2, 4, and 8 mg/ml) of G. glabra extract after 24, 48, and 72 h. 3-(4, 5-Dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide (MTT) test was used to evaluate the effects of the extract toxicity against T47D cells. Quantitative real-time polymerase chain reaction (PCR) technique was used to evaluate NM23 gene expression in T47D cells. Gas chromatography/mass spectrometry (GC/MS) analysis revealed that 28 different compounds were found in the G. glabra water extract. Among the chemical constituents defined, the dominant constituents were Benzeneacetic acid, 4-hydroxy-, methyl ester (27.35%), Thiophene, Tetrahydro-2-methyl- (11.42%), Mome-Inositol (9.91%), and 5-Tridecanone (4.73%). The percent of cell toxicity revealed that the effect of toxicity is related to the time and dose. The mRNA levels of NM23 gene expression were significantly increased in the T47D cells treated with IC50 concentration of G. glabra (P < 0.001, 30.33 fold). This amount in sub-IC50 concentration of the extract was 5.06 (p < 0.01) fold, showing a positive effect of the extract in enhancing the NM23 expression as compared to the control groups after 72 h. The result showed that G. glabra has the potential to cure breast cancer by enhancing NM23 expression. Therefore, it is suggested that more researches are needed to find some effective combinations in the plant to design new and effective drugs to treat cancer.

Keywords

References

Abolaji AO, Eteng MU, Ebong PE, Dar A, Farombi EO, Choudhary MI. 2014. Artemisia annua as a possible contraceptive agent: a clue from mammalian rat model. Nat Prod Res 28: 2342-46.
Chailungka A, Junpirom T, Pompimon W, Nuntasaen N, Meepowpan P. 2017. Two flavonoids first isolated from the seed of Syzygium nervosum and preliminary study of their anticancer and anti- HIV-1 reverse transcriptase activities.  Maejo Int J Sci Technol 11(01): 58-67.
Cheel J, Antwerpen PV, Tůmová L, Onofre G, Vokurková D, Zouaoui-Boudjeltia K,  Vanhaeverbeek M, Nève J. 2010.  Free radical-scavenging, antioxidant and immunostimulating effects of a licorice infusion (Glycyrrhiza glabra L.). Food Chem 122(3):508-517.
Chueh FS, Hsiao YT, Chang SJ, Wu PP, Lin JJ. 2012. Glycyrrhizic acid induces apoptosis in WEHI-3 mouse leukemia cells through the caspase-and mitochondriadependent pathways. Oncol Rep 28(6): 206976.
Colagar AH, Moradi Firouzjah H, Halalkhor S. 2015. Vitamin D receptor poly (A)-microsatellite polymorphism and serum levels of 25-hydroxyvitamin D: association with susceptibility to Breast cancer. J Breast Cancer 18(2): 119-125.
Darakhshan S, Bidmeshki Poura A, Colagar AH, Sisakhtnezhad S. 2015. Thymoquinone and its therapeutic potentials. Pharmacol Res 95-96: 138-158.
DeVita VT, Chu E. 2008. A history of cancer chemotherapy. Cancer Res 68(21): 8643-53.
Fu Y, Hsieh TC, Guo J. 2004. Licochalcone-A, a novel flavonoid isolated from licorice root (Glycyrrhiza glabra), causes G2 and late-G1 arrests in androgen-independent PC-3 prostate cancer cells.  Biochem Biophys Res Commun 322: 263-70.
Huang W, Tang S, Qiao X, Ma W, Ji S, Wang K, Ye M, Yu S. 2014. Isoangustone A induces apoptosis in SW480 human colorectal adenocarcinoma cells by disrupting mitochondrial functions. Fitoterapia 94: 36-47.
Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ. 2009. Cancer statistics. CA Cancer J Clin 55: 10-30.
Kinoshita T, Tamura Y, Mizutani K. 2005. The isolation and structure elucidation of minor isofl avonoids from licorice of Glycyrrhiza glabra origin. Chem Pharm Bull 53:847-49.
Lee SK, Park KK, Park JH, Lim SS, Chung WY. 2013. The inhibitory effect of roasted licorice extract on human metastatic breast cancer cell-induced bone destruction. Phytother Res 27(12): 1776-83.
Li S, Zhu JH, Cao LP, Sun Q, Liu HD, Li WD, Li JS. 2014. Growth inhibitory in vitro effects of glycyrrhizic acid in U251 glioblastoma cell line. Neurol 35(7): 1115-20.
Lorusso G, Rüegg C. 2012. New insights into the mechanisms of organ-specific breast cancer metastasis. Semin Cancer Biol 22(3): 226-33.
Mohadjerani M, Naqinezhad A; Aghasizadeh Sharbaf M. 2016. Platycladus orientalis extracts with antioxidant activity from north of Iran. J Genet Resour 2(2): 60-66
Neda GD, Rabeta MS. 2013. Chemical composition and anti-proliferative properties of flowers of Clitoria Ternatea. Int Food Res J 20(3): 1229-34.
Nezamabadi H, Rahimiyan Mashhadi H, Zand A, Alizadeh H. 2007. Investigation of some ecophysiological aspects of Licorice (Glycyrrhiza glabra) rhizome. Appl Entomol Phytopathol 74(2):45-62.
Park I, Park KK, Park JHY, Chung WY. 2009. Isoliquiritigenin induces G2 and M phase arrest by inducing DNA damage and by inhibiting the metaphase/anaphase transition. Cancer Lett 277(2): 174-81.
Prabhu V. 2012. Targeting Tumor Metastasis by Regulating NM23 Gene Expression. Asian Pacific J. Cancer Prev 13: 3539-48.
Pytel D, Sliwinski T. 2009. Tyrosine Kinase Blockers: New Hope for Successful Cancer Therapy. Anticancer Agents Med Chem 9 (1): 66-76.
Rafieian-Kopaei M, Setorki M, Doudi M, Baradaran A, Nasri H. 2014. Atherosclerosis: process, indicators, risk factors and new hopes. Int J Prev Med 5(8): 927-46.
Salehi S, Mirzaie A, Shandiz SAS, Noorbazargan H, Rahimi A, Yarmohammadi S, Ashrafi F. 2017. Chemical composition, antioxidant, antibacterial and cytotoxic effects of Artemisia marschalliana Sprengel extract. Nat Prod Res 31: 469-72.
Sharma H, Parihar L, Parihar P. 2011. Review on cancer and anticancerous properties of some medicinal plants. J Med Plants Res 5(10): 1818-35.
Sheela ML, Ramakrishna MK, Salimath BP. 2006. Angiogenic and proliferative effects of the cytokine VEGF in Ehrlich ascites tumor cells is inhibited by Glycyrrhiza glabra. Int Immunopharmacol 6(3): 494-8.
Shokri H. 2016. A review on the inhibitory potential of Nigella sativa against pathogenic and toxigenic fungi.  Avicenna J Phytomed 6(1): 21-33.
Siegel RL, Miller KD, Jemma A. 2015. Cancer statistics. CA Cancer J Clin 65(1): 5-29.
Singh SA, Bhat VS. 2011. Antimicrobial potential of 3-hydroxy-2-methylene-3-phenylpropionic acid derivatives.   Acta Pharm 61: 447-455.
Soltani N, Karami R, Ranjbar M. 2011.The interaction of salicylic acid and cold stress on antioxidant enzyme activities in licorice (Glycyrrhiza glabra). J Herbal Drugs 2(1): 7-13.
Walsh T, King MC. 2007.Ten genes for inherited breast cancer. Cancer Cell 11:103-5.
Wang ZY, Nixon DW. 2001. Licorice and cancer. Nutr Cancer 39:1-11.
Wei LS, Wee W, Siong JY, Syamsumir DF. 2011. Characterization of antimicrobial, antioxidant, anticancer properties and chemical composition of Sauropus androgynus stem extract.  Acta Med Litu 18(1): 12-16.
Yuan X, Li T, Xiao E, Zhao H, Li Y, Fu S, Wang Z. 2014. Licochalcone B inhibits growth of bladder cancer cells by arresting cell cycle progression and inducing apoptosis. Food Chem Toxicol 65: 242-251.
Zaidi SH, Huddart RA, Harrington KJ. 2009. Novel targeted radiosensitisers in cancer treatment. Curr Drug Discov Technol 6(2): 103-34.
Zhang JF, Li H, Li CQ, Tang HM, Yan RG. 2012. Effect of diammonium glycyrrhizinate on proliferation in liver cancer cell SMMC-7721 and p53 expression. Chongqing Med 41(27): 2852-2856.
 
 
Journal of Genetic Resources
Volume 3, Issue 1
March 2017
Pages 47-53

Files

Share

How to cite

Statistics