licochalcone-a and Glioma

Licochalcone A (LA), an active ingredient of licorice, has multiple biological activities, including antioxidative and anti-inflammatory activities. Although LA exerts antitumor effects in various cancer cells, its role in gliomas remains unclear. Therefore, this study determined whether LA inhibits glioma cell growth in vitro and in vivo. The present data revealed that LA effectively inhibited the growth of U87 glioma cells by inducing cell cycle arrest in the G0/G1 and G2/M phases; cell cycle arrest was attributed to the LA-mediated reduction of mRNA and protein levels of cyclins and cyclin-dependent kinases. Moreover, subcutaneous (flank) and orthotopic (brain) tumor models were used to determine the role of LA in gliomas. LA significantly alleviated tumor growth in both models. These findings indicate that LA exerts antitumor effects in gliomas in vitro and in vivo and that it is a potential agent for treating glioblastoma multiforme.

Topics: Animals; Antineoplastic Agents; Cell Cycle Checkpoints; Cell Line, Tumor; Cell Proliferation; Chalcones; Glioma; Humans; Male; Mice; Mice, Nude

Licochalcone A (LicA) has been reported to possess antitumor properties. However, its effect on human glioma cells remains unknown. In this study, we observed that LicA significantly suppressed the ADAM9 expression and the migration and invasion activities of human glioma cells (M059K, U-251 MG, and GBM8901) and exhibited no cell cytotoxicity. The human proteinase antibody array and immunoblot analysis indicated that the LicA treatment inhibited the expression of ADAM9 protein in human glioma cells. Recombinant human ADAM-9 (Rh-ADAM9) treatment significantly reversed the LicA-induced reduction in the ADAM9 level and the migration and invasion activities of human glioma cells. Additionally, the phosphorylation/activation of the mitogen-activated protein kinase kinase (MEK)-extracellularly responsive kinases (ERK) signaling pathway was significantly suppressed in LicA-treated human glioma cells. Cotreatment with LicA and PD98059 synergistically inhibited the ADAM9 expression, cell migration, and cell invasion, which suggested that the MEK-ERK signaling pathway was involved in the LicA-induced inhibition of the ADAM9 expression and the invasion activity of human glioma cells. These findings are the first evidence of LicA's anti-invasive properties against human glioma cells.

Topics: ADAM Proteins; Antineoplastic Agents; Cell Line, Tumor; Cell Movement; Chalcones; Extracellular Signal-Regulated MAP Kinases; Glioma; Humans; MAP Kinase Kinase Kinases; MAP Kinase Signaling System; Membrane Proteins; Neoplasm Invasiveness; Phosphorylation