Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells.
Licorice extracts containing glycyrrhizin exhibit anti-carcinogenic properties. Because glycyrrhizin induces severe hypokalemia and hypertension, we prepared a hexane/ethanol extract of Glycyrrhiza uralensis (HEGU) that lacks glycyrrhizin, and showed that HEGU induces apoptosis and G1 cell cycle arrest and inhibits migration of DU145 human prostate cancer cells. Our previous in vitro studies identified two active components in HEGU: isoangustone A, which induces apoptosis and G1 cycle arrest, and licoricidin, which inhibits metastasis. This study examined whether HEGU and licoricidin inhibit metastasis using the 4T1 mammary cancer model. Both HEGU and licoricidin treatment reduced pulmonary metastasis and the expression of CD45, CD31, HIF-1α, iNOS, COX-2, and VEGF-A in tumor tissues. Additionally, a decrease in protein expression of VEGF-R2, VEGF-C, VEGF-R3, and LYVE-1 was noted in tumor tissues of licoricidin-treated mice. Furthermore, the blood concentrations of MMP-9, ICAM-1, VCAM-1, and VEGF-A were decreased in HEGU-treated mice. In vitro 4T1 cell culture results showed that both HEGU and licoricidin inhibited cell migration, MMP-9 secretion, and VCAM expression. The present study demonstrates that the licoricidin in HEGU inhibits lung metastasis of 4T1 mammary carcinoma cells, which may be mediated via inhibition of cancer cell migration, tumor angiogenesis, and lymphangiogenesis.
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. young0122@hallym.ac.kr.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. young0122@hallym.ac.kr.
So Young
SY
Park
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. tnwls2022@naver.com.
Soo Jin
SJ
Kwon
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. limss@hallym.ac.kr.
Soon Sung
SS
Lim
Biocenter, Gyeonggi Institute of Science &amp; Technology Promotion, Suwon, Gyonggi-do 443-270, Korea. jinkyu90@gstep.re.kr.
Jin-Kyu
JK
Kim
Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. kiwon@snu.ac.kr.|WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea. kiwon@snu.ac.kr.|Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Korea. kiwon@snu.ac.kr.
Ki Won
KW
Lee
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. jyoon@hallym.ac.kr.|Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. jyoon@hallym.ac.kr.|Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Korea. jyoon@hallym.ac.kr.
Jung Han Yoon
JH
Park
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001578:Benzopyrans / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000097:blood; D002277:Carcinoma / Q000188:drug therapy* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000097:blood; D005260:Female; D006035:Glycyrrhiza / Q000737:chemistry*; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D061986:MCF-7 Cells; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D000970:Antineoplastic Agents; D001578:Benzopyrans; D014408:Biomarkers, Tumor; D010936:Plant Extracts; D019010:Vascular Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; C401293:licoricidin; D051546:Cyclooxygenase 2; D020780:Matrix Metalloproteinase 9
breast cancer; licorice extract; licoricidin; metastasis