Licorice root extracts have previously been shown to exhibit anti-carcinogenic activities. However, these extracts harbor considerable quantities of glycyrrhizin, which is known to exert anticarcinogenic activities and also to induce severe hypokalemia and hypertension. In our previous experiments, licoricidin was identified as an antimetastatic active component of a licorice root extract, which contains undetectable amounts of glycyrrhizin. In this study, we evaluated the effects of the licoricidin on the metastatic characteristics of 4T1 murine mammary carcinoma cells. When 4T1 cells were cultured on a transwell-filter in an in vitro model, licoricidin inhibited cell migration in a dose-dependent manner. Gelatin zymography and Western blot analysis showed that licoricidin significantly suppressed the secretion and activation of the matrix metalloproteinase (MMP)-2 and MMP-9. The secretion of tissue inhibitor of metalloproteinase-1 was reduced in licoricidin-treated cells. Licoricidin reduced the protein levels of vascular cell adhesion molecule but did not change intercellular adhesion molecule. To assess the effects of licoricidin on lung metastasis in vivo, we injected 4T1 cells (5×104 cells) into the inguinal mammary fat pads of syngeneic, immunocompetent BALB/c mice. Starting 1 week after 4T1 cell injection, the mice were given daily intraperitoneal injection of licoricidin (2 or 4 mg/kg body weight/day) for 21 days. Licoricidin treatment did not affect solid tumor growth but significantly reduced the number and volume of pulmonary tumor nodules. The expression of interleukin (IL)-1ra, IL-16, interferon γ-inducible protein (IP)-10, chemokine (C-X-C motif) ligand (CXCL)-9, MMP-3, -8, -9, osteopontin, pentraxin-3, stromal cell-derived factor (SDF)-1, and plasminogen activator inhibitor (PAI)-1 was increased in the lung tissues of mice injected with 4T1 cells, which was suppressed by the repeated injections of licoricidin. By contrast, the expression of angiopoietin-1, insulin-like growth factor binding proteins (IGFBP)-9 and IGFBP-10 was decreased in lung tissues of mice injected with 4T1 cells and was increased by the licoricidin treatment. In the present study, using both in vivo and in vitro systems, we have demonstrated that licoricidin profoundly inhibits the metastatic capacity of 4T1 mammary carcinoma cells, which may be mediated via the regulation of several metalloproteases, adhesion molecules, cytokines, and chemokines.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5239. doi:10.1158/1538-7445.AM2011-5239

©2011 American Association for Cancer Research
2011