Abstract 591: Licochalcone E inhibits solid tumor growth and lung metastasis of 4T1 murine mammary carcinoma cells in the BALB/c mouse orthotopic model

Abstract

Abstract Licochalcone E a phenolic constituent of licorice that is reported to exert excellent anti-cancer effects. In the present study, to investigate the effect of licochalcone E oral administration on the solid tumor growth and metastasis of breast cancer cells, 4T1 cells were injected into the inguinal mammary fat pads of syngeneic female BALB/c mice. One week after the injection the mice were subjected to oral gavage for 25 days with licochalcone E (0, 7, or 14 mg/kg body weight/day). Licochalcone E treatment induced a significant reduction in solid tumor growth, which was accompanied by 1) reduced Ki67 (prototypic cell cycle related nuclear antigen), cyclin-dependent kinase (CDK)2, CDK4, cyclin A, and cyclin D1 and 2) increased numbers of TUNEL-positive apoptotic cells with increased Bax and cleaved caspase-3 expression but reduced Bcl-2 expression in tumor tissues. Licochalcone E also reduced the expression of hypoxia inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), VEGF-R2, CD31 (platelet endothelial cell adhesion molecule-1), VEGF-C and LYVE-1 (lymphatic vessel endothelial receptor-) in tumor tissues. In addition to tumor growth, oral licochalcone E administration markedly reduced the number of pulmonary tumor nodules. In lung tissues, licochalcone E induced a significant reduction in the levels of cytokines and angiogenesis-related proteins including DPPIV (CD26), endoglin (CD105), MMP-9, C5a, interleukin (IL)-1ra, IL-16, MIG (CXCL9). In vitro culture studies showed that licochalcone E dose-dependently inhibited the migration of MDA-MB-231 human breast cancer cells at concentrations of 0-20 μmol/L without significant changes in cell viability. Licochalcone E significantly reduced secretion of matrix metalloproteinase-9, urokinase-type plasminogen activator and VEGF in concentration-dependent manners in MDA-MB-231 cells. These results demonstrated that licochalcone E inhibits solid tumor growth and metastasis of breast cancer cells and these effects were mediated via the reduction of a wide variety of cytokines and chemokines, which subsequently inhibits tumor angiogenesis, lymphangiogenesis, proliferation, and metastasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 591. doi:1538-7445.AM2012-591