Skip to main content
×
Home

Hexane–ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells

  • So Young Park (a1), Soon Sung Lim (a1), Jin Kyu Kim (a2), Il-Jun Kang (a1), Jong-Sang Kim (a3), Choonghwan Lee (a4), Jongdai Kim (a5) (a6) and Jung Han Yoon Park (a1) (a5)...
Abstract

Licorice extracts are known to exhibit anti-carcinogenic activities. However, chronic licorice consumption can lead to serious side effects due to the presence of considerable quantities of glycyrrhizin, which causes severe hypokalaemia and hypertension. In the present study, we evaluated the effects of a hexane–ethanol extract of Glycyrrhiza uralensis (HEGU), which lacks glycyrrhizin, on the metastatic characteristics of DU145 prostate cancer cells. HEGU inhibited basal and epidermal growth factor-induced cell migration, invasion and adhesion in a dose-dependent fashion. HEGU significantly suppressed the secretion and activation of the matrix metalloproteinase (MMP)-2 and MMP-9. The secretion of tissue inhibitor of metalloproteinase (TIMP)-1 was reduced, but that of TIMP-2 was increased in HEGU-treated cells. HEGU reduced the protein levels of integrin-α2, the intercellular adhesion molecule, and the vascular cell adhesion molecule. An active fraction of HEGU was separated via column chromatography, and the structure of the active component, licoricidin, was identified via 1H NMR and 13C NMR. The treatment of DU145 cells with licoricidin induced a reduction in cell migration and the secretion of MMP-9, TIMP-1, urokinase-type plasminogen activator and vascular endothelial growth factor, as well as in the expression of adhesion molecules. These results indicate that HEGU, which contains licoricidin, is a potent anti-metastatic agent, which can markedly inhibit the metastatic and invasive capacity of malignant prostate cancer cells. The observed reductions in the activation of proteases and the levels of adhesion molecules may constitute a component of the mechanisms by which HEGU inhibits the migration and adhesion of prostate cancer cells.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Hexane–ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells
      Available formats
      ×
      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Dropbox account. Find out more about sending content to Dropbox.

      Hexane–ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells
      Available formats
      ×
      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your Google Drive account. Find out more about sending content to Google Drive.

      Hexane–ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells
      Available formats
      ×
Copyright
Corresponding author
*Corresponding author: J. H. Y. Park, fax +82 33 256 0199, email jyoon@hallym.ac.kr
References
Hide All
1 Lee CK, Park KK, Lim SS, et al. (2007) Effects of the licorice extract against tumor growth and cisplatin-induced toxicity in a mouse xenograft model of colon cancer. Biol Pharm Bull 30, 21912195.
2 Adams LS, Seeram NP, Hardy ML, et al. (2006) Analysis of the interactions of botanical extract combinations against the viability of prostate cancer cell lines. Evid Based Complement Alternat Med 3, 117124.
3 Jo EH, Kim SH, Ra JC, et al. (2005) Chemopreventive properties of the ethanol extract of chinese licorice (Glycyrrhiza uralensis) root: induction of apoptosis and G1 cell cycle arrest in MCF-7 human breast cancer cells. Cancer Lett 230, 239247.
4 Ma J, Peng W & Liang D (2000) Apoptosis of human gastric cancer cell line MGC-803 induced by Glycyrrhiza uralensis extract. Zhongguo Zhong Xi Yi Jie He Za Zhi 20, 928930.
5 Wang ZY & Nixon DW (2001) Licorice and cancer. Nutr Cancer 39, 111.
6 Asl MN & Hosseinzadeh H (2008) Review of pharmacological effects of Glycyrrhiza sp. and its bioactive compounds. Phytother Res 22, 709724.
7 Kobayashi M, Fujita K, Katakura T, et al. (2002) Inhibitory effect of glycyrrhizin on experimental pulmonary metastasis in mice inoculated with B16 melanoma. Anticancer Res 22, 40534058.
8 Hibasami H, Iwase H, Yoshioka K, et al. (2005) Glycyrrhizin induces apoptosis in human stomach cancer KATO III and human promyelotic leukemia HL-60 cells. Int J Mol Med 16, 233236.
9 Hibasami H, Iwase H, Yoshioka K, et al. (2006) Glycyrrhetic acid (a metabolic substance and aglycon of glycyrrhizin) induces apoptosis in human hepatoma, promyelotic leukemia and stomach cancer cells. Int J Mol Med 17, 215219.
10 Thirugnanam S, Xu L, Ramaswamy K, et al. (2008) Glycyrrhizin induces apoptosis in prostate cancer cell lines DU-145 and LNCaP. Oncol Rep 20, 13871392.
11 Hattori M, Sakamoto T, Kobashi K, et al. (1983) Metabolism of glycyrrhizin by human intestinal flora. Planta Med 48, 3842.
12 Stormer FC, Reistad R & Alexander J (1993) Glycyrrhizic acid in liquorice – evaluation of health hazard. Food Chem Toxicol 31, 303312.
13 van Uum SH (2005) Liquorice and hypertension. Neth J Med 63, 119120.
14 Choi HJ, Seon MR, Lim SS, et al. (2008) Hexane/ethanol extract of Glycyrrhiza uralensis licorice suppresses doxorubicin-induced apoptosis in H9c2 rat cardiac myoblasts. Exp Biol Med 233, 15541560.
15 Jemal A, Siegel R, Ward E, et al. (2008) Cancer statistics, 2008. CA Cancer J Clin 58, 7196.
16 Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12, 895904.
17 Bogenrieder T & Herlyn M (2003) Axis of evil: molecular mechanisms of cancer metastasis. Oncogene 22, 65246536.
18 Yoon SO, Park SJ, Yun CH, et al. (2003) Roles of matrix metalloproteinases in tumor metastasis and angiogenesis. J Biochem Mol Biol 36, 128137.
19 Zhang L, Shi J, Feng J, et al. (2004) Type IV collagenase (matrix metalloproteinase-2 and -9) in prostate cancer. Prostate Cancer Prostatic Dis 7, 327332.
20 Crippa MP (2007) Urokinase-type plasminogen activator. Int J Biochem Cell Biol 39, 690694.
21 Orian-Rousseau V & Ponta H (2008) Adhesion proteins meet receptors: a common theme? Adv Cancer Res 101, 6392.
22 Okegawa T, Pong RC, Li Y, et al. (2004) The role of cell adhesion molecule in cancer progression and its application in cancer therapy. Acta Biochim Pol 51, 445457.
23 Moll UM, Youngleib GL, Rosinski KB, et al. (1990) Tumor promoter-stimulated Mr 92,000 gelatinase secreted by normal and malignant human cells: isolation and characterization of the enzyme from HT1080 tumor cells. Cancer Res 50, 61626170.
24 Azzam HS & Thompson EW (1992) Collagen-induced activation of the M(r) 72,000 type IV collagenase in normal and malignant human fibroblastoid cells. Cancer Res 52, 45404544.
25 Cho HJ, Kim WK, Kim EJ, et al. (2003) Conjugated linoleic acid inhibits cell proliferation and ErbB3 signaling in HT-29 human colon cell line. Am J Physiol Gastrointest Liver Physiol 284, G9961005.
26 Kwon GT, Cho HJ, Chung WY, et al. (2009) Isoliquiritigenin inhibits migration and invasion of prostate cancer cells: possible mediation by decreased JNK/AP-1 signaling. J Nutr Biochem 20, 663676.
27 Howard EW, Bullen EC & Banda MJ (1991) Regulation of the autoactivation of human 72-kDa progelatinase by tissue inhibitor of metalloproteinases-2. J Biol Chem 266, 1306413069.
28 Li Y & Cozzi PJ (2007) Targeting uPA/uPAR in prostate cancer. Cancer Treat Rev 33, 521527.
29 Fukai T, Toyono M & Nomura T (1988) On the structure of licoricidin. Heterocycles 27, 23092313.
30 Cho HJ, Lim SS, Lee YS, et al. (2010) Hexane/ethanol extract of Glycyrrhiza uralensis licorice exerts potent anti-inflammatory effects in murine macrophages and in mouse skin. Food Chem 121, 959966.
31 Hawthorne S & Gallagher S (2008) Effects of glycyrrhetinic acid and liquorice extract on cell proliferation and prostate-specific antigen secretion in LNCaP prostate cancer cells. J Pharm Pharmacol 60, 661666.
32 Shibata S, Inoue H, Iwata S, et al. (1991) Inhibitory effects of licochalcone A isolated from Glycyrrhiza inflata root on inflammatory ear edema and tumour promotion in mice. Planta Med 57, 221224.
33 Yamazaki S, Morita T, Endo H, et al. (2002) Isoliquiritigenin suppresses pulmonary metastasis of mouse renal cell carcinoma. Cancer Lett 183, 2330.
34 Agarwal MK, Iqbal M & Athar M (2005) Inhibitory effect of 18beta-glycyrrhetinic acid on 12-O-tetradecanoyl phorbol-13-acetate-induced cutaneous oxidative stress and tumor promotion in mice. Redox Rep 10, 151157.
35 Fukai T, Marumo A, Kaitou K, et al. (2002) Anti-Helicobacter pylori flavonoids from licorice extract. Life Sci 71, 14491463.
36 Hatano T, Kusuda M, Inada K, et al. (2005) Effects of tannins and related polyphenols on methicillin-resistant Staphylococcus aureus. Phytochemistry 66, 20472055.
37 Lambert E, Dasse E, Haye B, et al. (2004) TIMPs as multifacial proteins. Crit Rev Oncol Hematol 49, 187198.
38 Jiang Y, Goldberg ID & Shi YE (2002) Complex roles of tissue inhibitors of metalloproteinases in cancer. Oncogene 21, 22452252.
39 Soula-Rothhut M, Coissard C, Sartelet H, et al. (2005) The tumor suppressor PTEN inhibits EGF-induced TSP-1 and TIMP-1 expression in FTC-133 thyroid carcinoma cells. Exp Cell Res 304, 187201.
40 Honkavuori M, Talvensaari-Mattila A, Puistola U, et al. (2008) High serum TIMP-1 is associated with adverse prognosis in endometrial carcinoma. Anticancer Res 28, 27152719.
41 Blasi F & Verde P (1990) Urokinase-dependent cell surface proteolysis and cancer. Semin Cancer Biol 1, 117126.
42 Folkman J (2002) Role of angiogenesis in tumor growth and metastasis. Semin Oncol 29, 1518.
43 Hicklin DJ & Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23, 10111027.
44 Goh PP, Sze DM & Roufogalis BD (2007) Molecular and cellular regulators of cancer angiogenesis. Curr Cancer Drug Targets 7, 743758.
45 Christofori G (2006) New signals from the invasive front. Nature 441, 444450.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Full text views

Total number of HTML views: 11
Total number of PDF views: 89 *
Loading metrics...

Abstract views

Total abstract views: 141 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 24th November 2017. This data will be updated every 24 hours.