title: Arctigenin, a lignan from Arctium lappa L., inhibits metastasis of human breast cancer cells through the downregulation of MMP-2/-9 and heparanase in MDA-MB-231 cells.
abstract: Arctigenin is a bioactive lignan isolated from the seeds of Arctium lappa L. which has been widely used as a diuretic and a diaphoretic in Traditional Chinese Medicine. In the present study, the authors investigated the effects of arctigenin on tumor migration and invasion in aggressive human breast cancer cells. The MTT assay results showed that arctigenin did not show a significant cytotoxic effect on the cell viability of MDA-MB-231 cells. However, wound healing migration and Boyden chamber invasion assays demonstrated that arctigenin significantly inhibited in vitro migration and invasion of the MDA-MB-231 cells. Furthermore, gelatin zymography results showed that arctigenin reduced the activity of MMP-2 and MMP-9. Western blot analysis results demonstrated that the expression of MMP-2, MMP-9 and heparanase proteins was significantly downregulated following the treatment of arctigenin. Finally, the antiangiogenic activity of arctigenin was also examined by the chick embryo chorioallantoic membrane (CAM) assay. Arctigenin treatment significantly inhibited angiogenesis in the CAM. In conclusion, the results revealed that arctigenin significantly inhibited the migration and invasion of MDA-MB-231 cells by downregulating MMP-2, MMP-9 and heparanase expression. However, further studies are still necessary to investigate the exact mechanisms involved and to explore signal transduction pathways to better understand the biological mechanisms.
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Binjiang, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Chenghua
authors.initials: C
authors.lastname: Lou
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Binjiang, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Binjiang, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Yaping
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Binjiang, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhu
authors.affiliation: College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Binjiang, Hangzhou, Zhejiang 310053, P.R. China.
authors.forename: Huajun
authors.initials: H
authors.lastname: Zhao
mesh_terms: D000818:Animals; D031170:Arctium / Q000737:chemistry; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D002642:Chick Embryo; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics; D005260:Female; D005663:Furans / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005966:Glucuronidase / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D017705:Lignans / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000235:genetics* / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000378:metabolism; D009362:Neoplasm Metastasis; D000099175:Heparanase
chemical_list: D005663:Furans; D005966:Glucuronidase; D017705:Lignans; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D000099175:Heparanase; C522361:MMP2 protein, human; C579270:MMP9 protein, human; C071942:arctigenin