Effect of Root Extracts of Medicinal Herb Glycyrrhiza glabra on HSP90 Gene Expression and Apoptosis in the HT-29 Colon Cancer Cell Line

  • Nourazarian, Seyed Manuchehr (Department of Laboratory Sciences, Faculty of Paramedical Sciences, Tabriz University of Medical Sciences) ;
  • Nourazarian, Alireza (Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences) ;
  • Majidinia, Maryam (Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences) ;
  • Roshaniasl, Elmira (Department of Biochemistry, Faculty of Medicine, Urmia University of Medical Sciences)
  • Published : 2016.01.11


Colorectal cancer is one of the most common lethal cancer types worldwide. In recent years, widespread and large-scale studies have been done on medicinal plants for anti-cancer effects, including Glycyrrhiza glabra. The aim of this study was to evaluate the effects of an ethanol extract Glycyrrhiza glabra on the expression of HSP90, growth and apoptosis in the HT-29 colon cancer cell line. HT-29 cells were treated with different concentrations of extract (50,100,150, and $200{\mu}g/ml$). For evaluation of cell proliferation and apoptosis, we used MTT assay and flow cytometry technique, respectively. RT-PCR was also carried out to evaluate the expression levels of HSP90 genes. Results showed that Glycyrrhiza glabra inhibited proliferation of the HT-29 cell line at a concentration of $200{\mu}g/ml$ and this was confirmed by the highest rate of cell death as measured by trypan blue and MTT assays. RT-PCR results showed down-regulation of HSP90 gene expression which implied an ability of Glycyrrhiza glabra to induce apoptosis in HT-29 cells and confirmed its anticancer property. Further studies are required to evaluate effects of the extract on other genes and also it is necessary to make an extensive in vivo biological evaluation and subsequently proceed with clinical evaluations.


  1. Chu XT, De la Cruz J, Hwang SG, Hong H (2014). Tumorigenic effects of endocrine-disrupting chemicals are alleviated by licorice (Glycyrrhiza glabra) root extract through suppression of AhR expression in mammalian cells. Asian Pac J Cancer Prev, 15, 4809-13.
  2. Cooper L (2011). The role of Hsp90 in the Wnt pathway of MCF7 breast cancer cells. Masters, Rhodes University.
  3. Crage G, Newman D, Snader K (1997). Natural products in drug discovery and development. J Natural Products, 60, 52-60.
  4. Dobo C, Stavale JN, Lima FO(2013). HSP27 is Commonly Expressed in Cervical Intraepithelial Lesions of Brazilian Women. Asian Pac J Cancer Prev, 14, 5007-10.
  5. Dong S, Inoue A, Zhu Y, Tanji M, Kiyama R (2007). Activation of rapid signaling pathways and the subsequent transcriptional regulation for the proliferation of breast cancer MCF-7 cells by the treatment with an extract of Glycyrrhiza glabra root." Food Chemical Toxicol, 45, 2470-8.
  6. Drecoll E, Nitsche U, Bauer K, et al (2014). Expression analysis of heat shock protein 90 (HSP90) and Her2 in colon carcinoma. Int J Colorectal Dis, 29, 663-71.
  7. Foster FM , Streuli CH (2006). Inhibitor of apoptosis proteins in breast cancer. Breast Can Res, 8, 9.
  8. Fu Y, Hsieh TC, Guo J, et al (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, 263-270.
  9. Gholamhoseinian Najar A, Pashaei-Asl R, Omidi Y, Farajnia S, Nourazarian AR (2013). EGFR antisense oligonucleotides encapsulated with nanoparticles decrease egfr, mapk1 and stat5 expression in a human colon cancer cell line. Asian Pac J Cancer Prev, 14, 495-8.
  10. Hall AJ, Forsberg LK, Blagg SJ (2014). Alternative approaches to Hsp90 modulation for the treatment of cancer. Future Med Chem, 6, 1587-1605.
  11. Haupt A, Joberty G, Bantscheff M, Frohlich H (2012). Hsp90 inhibition differentially destabilises MAPkinase and TGFbeta signalling components in cancer cells revealed by kinase-targeted chemoproteomic. BMC Cancer, 12, 1-12.
  12. Li H, Zhu F, Boardman LA, et al (2015). Aspirin prevents colorectal cancer by Normalizing EGFR Expression. EBio Med, 2, 447-55.
  13. Mamede AC, Laranjo M, Carvalho MJ (2014). Effect of amniotic membrane proteins in human cancer cell lines: an exploratory study. J Membr Biol, 247, 357-60.
  14. Moser C, Lang S, Stoeltzing O (2009). Heat-shock Protein 90 (Hsp90) as a molecular target for therapy of gastrointestinal cancer. Anticancer Res, 29, 2031-42.
  15. Nagaraj SA, Lingaraj SM, Balaraju Y, Kumar A, Salimath BP (2012). MTA1 induced angiogenesis, migration and tumor growth is inhibited by Glycyrrhiza glabra. IOSR J Pharmacy, 2, 34-43.
  16. Nakagawa K, Kishida H, Arai N, Nishiyama T, Mae T(2004). Licorice flavonoids suppress abdominal fat accumulation and increase in blood glucose level in obese diabetic KK-A(y) mic. Biol Pharm Bull, 27, 1775-8.
  17. Niknejad H, Khayat-Khoei M, Peirovi H, Abolghasemi H (2014). Human amniotic epithelial cells induce apoptosis of cancer cells: a new anti-tumor therapeutic strategy. Cytotherapy, 16, 33-40.
  18. Nobili S, Lippi D, Witort E, Donnini M, Bausi L (2009). Natural compounds for cancer treatment and prevention." Pharmacological Res, 59, 365-78.
  19. Nourazarian AR, Kangari P, Salmaninejad A (2014). Roles of oxidative stress in the development and progression of breast cancer. Asian Pac J Cancer Prev, 15, 4745-51.
  20. Porter JR, Fritz CC, Depew KM (2010). Discovery and development of Hsp90 inhibitors: a promising pathway for cancer therapy. Curr Opin Chem Biol, 14, 412-420.
  21. Rajandeep K, Karan K, Harpreet K (2011). Plants as asource of anticancer agents. J Nat Prod Plant Resour, 1, 119-24.
  22. 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, 494-498.
  23. Vickers A (2002). Botanical medicines for the treatment of cancer: rationale, overview of current data, and methodological considerations for phase I and II trials. Cancer Invest, 20, 1069-79.
  24. Visavadiya NP, Soni B, Dalwadi N (2009). Evaluation of antioxidant and anti-atherogenic properties of Glycyrrhiza glabra root using in vitro models. Int J Food Sci Nutr, 2, 135-49.
  25. Yano M, Naito Z, Tanaka S, Asano G (1996). Expression and roles of heat shock proteins in human breast cancer. Jpn J Cancer Res, 87, 908-15.

Cited by

  1. Cordyceps militaris induces tumor cell death via the caspase-dependent mitochondrial pathway in HepG2 and MCF-7 cells vol.13, pp.6, 2016,
  2. (Licorice): A Review vol.31, pp.11, 2017,
  3. Effective Medicinal Plant in Cancer Treatment, Part 2 pp.2156-5899, 2017,
  4. Quercetin: A functional dietary flavonoid with potential chemo-preventive properties in colorectal cancer vol.233, pp.9, 2018,