title: Inhibitory effects of GL-V9 on the invasion of human breast carcinoma cells by downregulating the expression and activity of matrix metalloproteinase-2/9.
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.
authors.affiliation: Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Tongjiaxiang, Nanjing, People's Republic of China.
authors.forename: Liwen
authors.initials: L
authors.lastname: Li
authors.forename: Pu
authors.initials: P
authors.lastname: Chen
authors.forename: Yun
authors.initials: Y
authors.lastname: Ling
authors.forename: Xiuming
authors.initials: X
authors.lastname: Song
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Lu
authors.forename: Qinghao
authors.initials: Q
authors.lastname: He
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Lu
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D005260:Female; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000517:prevention & control*; D010766:Phosphorylation
chemical_list: C561826:5-hydroxy-8-methoxy-2-phenyl-7-(4-(pyrrolidin-1-yl)butoxy)4H-chromen-4-one; D005419:Flavonoids; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9