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Abstract: Matrix metalloproteinases (MMPs) play important roles in the invasion and migration of cancer cells. In this study, we used in vitro and in vivo assays to examine the inhibitory effects of oroxylin A, one of the main bioactive flavonoid extracted from Scutellaria radix, on the human breast carcinoma cell MDA-MB-231 invasion and migration. We found that oroxylin A can suppress cell adhesion, invasion and migration in a concentration-dependent manner. Moreover, oroxylin A led to the reduction of the activity and expression levels of MMP-2 and MMP-9 in gelatin zymography, real-time PCR and western blotting analysis. Further elucidation of the mechanism revealed that oroxylin A increased the expression of tissue inhibitor of metalloproteinase-2 (TIMP-2), the endogenous inhibitor of MMP-2, and repressed the phorbol-12-myristate-13-acetate (PMA)-induced translocation of protein kinase Cδ (PKCδ), phosphorylation of extracellular signal-regulated kinase (ERK1/2) and binding activity of the transcription factor activator protein-1 (AP-1) which are upstream signaling molecules in MMP-9 expression. Our results also indicated that oroxylin A inhibited the lung metastasis of murine melanoma cell B16-F10 in vivo. Therefore, we proposed that oroxylin A might be developed as a therapeutic potential candidate for the treatment of cancer metastasis. [Copyright &y& Elsevier]

Abstract: It has been well characterized that flavonoids possess pronounced anticancer potentials including anti-angiogenesis, anti-metastasis, and pro-apoptosis. Herein, we report, for the first time, that VI-14, a novel flavonoid derivative, possesses anti-cancer properties. The purpose of this study is to investigate the anti-migration and anti-invasion activities of VI-14 in breast cancer cells. Our data indicate that VI-14 inhibits adhesion, migration and invasion of MDA-MB-231 and MDA-MB-435 human breast cancer cells. MDA-MB-231 cells treated with VI-14 display reduced activities and expressions of ECM degradation-associated proteins including matrix metalloproteinase 2 (MMP-2) and 9 (MMP-9) at both the protein and mRNA levels. Meanwhile, VI-14 treatment induces an up-regulated expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) and 2 (TIMP-2) in MDA-MB-231 cells. Western blotting results show that phosphorylation levels of critical components of the MAPK signaling pathway, including ERK, JNK and P38, are dramatically decreased in VI-14-treated MDA-MB-231 cells. Furthermore, treatment of VI-14 significantly decreases the nuclear levels and the binding ability of nuclear factor-kappa B (NF-κB) and activator protein-1 (AP-1). Taken together, our data suggest that VI-14 treatment suppresses migration and motility of breast cancer cells, and VI-14 may be a potential compound for cancer therapy. [Copyright &y& Elsevier]

Abstract: Cancer cell invasion plays a crucial role in growth and local spreading of tumors. GL-V9 is a newly synthesized flavonoid that has been shown to possess an antitumor effect. However, the mechanism of GL-V9 in preventing tumor growth is still unclear. The purpose of this study is to investigate the anti-invasive and anti-metastatic activity of this novel compound in MDA-MB-231 and MCF-7 human breast carcinoma cells. In this study, GL-V9 caused a concentration-dependent suppression of cell adhesive ability by cell adhesion assay, it also inhibited the migration and invasion of cells by wound healing assay and transwell invasion assay in a concentration-dependent manner. Considering matrix metalloproteinases (MMPs) play an important role in metastatic process, we used western blotting and gelatin zymography to examine the effect of GL-V9 on the expression and activity of MMPs. The mechanism revealed that GL-V9 significantly suppressed the expression and activity of MMP-2 and MMP-9. Furthermore, GL-V9 suppressed their upstream protein kinases activation by reducing phosphorylated forms of serine/threonine kinase AKT and c-Jun N-terminal kinase. These findings suggested that GL-V9 could inhibit the invasion of tumor cells by downregulating the expression and activity of MMP-2 and MMP-9, potentially associating with the suppression of phosphorylation of AKT and JNK. [Copyright &y& Elsevier]