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Int J Mol Sci. 2016 Jun 14;17(6). pii: E934. doi: 10.3390/ijms17060934.

Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells.

Park SY1,2, Kwon SJ3, Lim SS4, Kim JK5, Lee KW6,7,8, Park JH9,10,11.

Author information

1
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. young0122@hallym.ac.kr.
2
Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. young0122@hallym.ac.kr.
3
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. tnwls2022@naver.com.
4
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. limss@hallym.ac.kr.
5
Biocenter, Gyeonggi Institute of Science & Technology Promotion, Suwon, Gyonggi-do 443-270, Korea. jinkyu90@gstep.re.kr.
6
Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. kiwon@snu.ac.kr.
7
WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea. kiwon@snu.ac.kr.
8
Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Korea. kiwon@snu.ac.kr.
9
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea. jyoon@hallym.ac.kr.
10
Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea. jyoon@hallym.ac.kr.
11
Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Korea. jyoon@hallym.ac.kr.

Abstract

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.

KEYWORDS:

breast cancer; licorice extract; licoricidin; metastasis

PMID:
27314329
PMCID:
PMC4926467
DOI:
10.3390/ijms17060934
[Indexed for MEDLINE]
Free PMC Article

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