Int. J. Mol. Sci. 2016, 17(6), 934; https://doi.org/10.3390/ijms17060934
Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells
So Young Park 1,2, Soo Jin Kwon 1, Soon Sung Lim 1
, Jin-Kyu Kim 3, Ki Won Lee 2,4,5 and Jung Han Yoon Park 1,2,5,*
, Jin-Kyu Kim 3, Ki Won Lee 2,4,5 and Jung Han Yoon Park 1,2,5,*
1
Department of Food Science and Nutrition, Hallym University, Chuncheon 200-702, Korea
2
Advanced Institutes of Convergence Technology, Seoul National University, Suwon, Gyonggi-do 443-270, Korea
3
Biocenter, Gyeonggi Institute of Science & Technology Promotion, Suwon, Gyonggi-do 443-270, Korea
4
WCU Biomodulation Major, Department of Agricultural Biotechnology and Center for Food and Bioconvergence, Seoul National University, Seoul 151-921, Korea
5
Research Institute of Agriculture and Life Sciences, Seoul National University, Seoul 151-742, Korea
*
Author to whom correspondence should be addressed.
Academic Editor: Gopinadhan Paliyath
Received: 15 April 2016 / Revised: 6 June 2016 / Accepted: 8 June 2016 / Published: 14 June 2016
(This article belongs to the Special Issue The Mechanism of Action of Food Components in Disease Prevention)
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. View Full-TextKeywords:
licorice extract; licoricidin; metastasis; breast cancer
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Park, S.Y.; Kwon, S.J.; Lim, S.S.; Kim, J.-K.; Lee, K.W.; Park, J.H.Y. Licoricidin, an Active Compound in the Hexane/Ethanol Extract of Glycyrrhiza uralensis, Inhibits Lung Metastasis of 4T1 Murine Mammary Carcinoma Cells. Int. J. Mol. Sci. 2016, 17, 934.
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