Licochalcone E present in licorice suppresses lung metastasis in the 4T1 mammary orthotopic cancer model.

Abstract

We investigated whether licochalcone E (LicE), a phenolic constituent of licorice, inhibits mammary tumor growth and metastasis using animal and cell culture models. 4T1 mammary carcinoma cells were injected into the mammary fat pads of syngeneic BALB/c mice. Starting 7 days after the injection, the mice received LicE (7 or 14 mg/kg body weight/day) via oral gavage for 25 days. LicE suppressed solid tumor growth and lung metastasis, but did not exhibit kidney or liver toxicity. In tumor tissues, LicE treatment induced a reduction in the expression of Ki67, cyclins, and cyclin-dependent kinases and stimulated apoptosis with increased expression of Bax and cleaved caspase-3 but decreased expression of Bcl-2. In addition, LicE decreased expression of CD31, vascular endothelial growth factor (VEGF)-A and C, VEGF-receptor 2, lymphatic vessel endothelial receptor-1, CD45, cyclooxygenase-2, inducible nitric oxide synthase, and hypoxia inducible factor-1α in tumor tissues. In lung tissues, LicE reduced the levels of proinflammatory cytokines and angiogenesis/metastasis-related proteins. In mammary cancer cell cultures, LicE (5-20 μmol/L) dose dependently inhibited cell migration and invasion. LicE inhibited secretion of matrix metalloproteinase-9, urokinase-type plasminogen activator and VEGF-A, and stimulated secretion of tissue inhibitor of metalloproteinase-2 in MDA-MB-231 cells. In addition, LicE inhibited tube formation of vascular endothelial cells. We show that LicE administration suppressed tumor growth and lung metastasis in the mouse model in conjunction with LicE inhibition of cell migration, invasion, and tube formation in vitro. Reduced tumor growth and metastasis in LicE-treated mice may be, at least in part, attributed to reduced inflammation and tumor angiogenesis.

• Authors: Soo Jin Kwon, So Young Park, Gyoo Taik Kwon, Ki Won Lee, Young-Hee Kang, Myung-Sook Choi, Jong Won Yun, Jae-Ho Jeon, Jong Gab Jun, Jung Han Yoon Park
• Journal: Cancer prevention research (Philadelphia, Pa.) (Cancer Prev Res (Phila)) Vol. 6 Issue 6 Pg. 603-13 (Jun 2013) ISSN: 1940-6215 [Electronic] United States
• PMID: 23625311 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers, Tumor
• Chalcones
• licochalcone E

Topics

• Animals
• Apoptosis (drug effects)
• Biomarkers, Tumor (analysis)
• Blotting, Western
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Adhesion (drug effects)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Chalcones (pharmacology)
• Female
• Flow Cytometry
• Fluorescent Antibody Technique
• Glycyrrhiza (chemistry)
• Humans
• Immunoenzyme Techniques
• Lung Neoplasms (metabolism, prevention & control, secondary)
• Mammary Neoplasms, Experimental (metabolism, pathology, prevention & control)
• Mice
• Mice, Inbred BALB C
• Neovascularization, Pathologic (prevention & control)
• Plant Roots (chemistry)
• Tumor Cells, Cultured