Hexane-ethanol extract of Glycyrrhiza uralensis containing licoricidin inhibits the metastatic capacity of DU145 human prostate cancer cells.
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.
Park
So Young
SY
Department of Food Science and Nutrition, Hallym University, 39 Hallymdaehak-gil, Chuncheon 200-702, South Korea.
Lim
Soon Sung
SS
Kim
Jin Kyu
JK
Kang
Il-Jun
IJ
Kim
Jong-Sang
JS
Lee
Choonghwan
C
Kim
Jongdai
J
Park
Jung Han Yoon
JH
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D029882:Glycyrrhiza uralensis / Q000737:chemistry*; D006801:Humans; D039001:Integrin alpha Chains / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D009361:Neoplasm Invasiveness; D010447:Peptide Hydrolases / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D018517:Plant Roots; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D001578:Benzopyrans; D015815:Cell Adhesion Molecules; D039001:Integrin alpha Chains; D036341:Intercellular Signaling Peptides and Proteins; D010936:Plant Extracts; C401293:licoricidin; D010447:Peptide Hydrolases