British Journal of Nutrition

Full Papers

Molecular Nutrition

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

So Young Parka1, Soon Sung Lima1, Jin Kyu Kima2, Il-Jun Kanga1, Jong-Sang Kima3, Choonghwan Leea4, Jongdai Kima5a6 and Jung Han Yoon Parka1a5 c1

a1 Department of Food Science and Nutrition, Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, South Korea

a2 Institute of Natural Medicine, Hallym University, Chuncheon 200-702, South Korea

a3 Department of Animal Science and Biotechnology, Kyungpook National University, Daegu 702-701, South Korea

a4 Division of Bioscience and Biotechnology, Konkuk University, Seoul 143-701, South Korea

a5 Medical and Bio-Materials Research Center, Kangwon National University, Chuncheon 200-701, South Korea

a6 Department of Food Science and Biotechnology, Kangwon National University, Chuncheon 200-701, South Korea

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.

(Received November 30 2009)

(Revised March 18 2010)

(Accepted April 13 2010)

(Online publication May 21 2010)

Correspondence:

c1 Corresponding author: J. H. Y. Park, fax +82 33 256 0199, email jyoon@hallym.ac.kr

Footnotes

Abbreviations: DMEM, Dulbecco's modified Eagle's medium; EGF, epidermal growth factor; FBS, fetal bovine serum; HEGU, hexane–ethanol extract of Glycyrrhiza uralensis; ICAM, intercellular adhesion molecule; MMP, matrix metalloproteinase; Mr, molecular weight; TIMP, tissue inhibitor of metalloproteinase; uPA, urokinase-type plasminogen activator; VCAM, vascular cell adhesion molecule; VEGF, vascular endothelial growth factor

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