title: Brazilein suppresses migration and invasion of MDA-MB-231 breast cancer cells.
abstract: Brazilein, a bioactive compound isolated from Caesalpinia sappan L., has long been used in oriental folk medicines. Cancer metastasis is a primary cause of cancer death. However, the anti-metastatic effects of brazilein remain elusive. In this study, we found that brazilein inhibited human breast cancer MDA-MB-231 cell migration and invasion using wound-healing assay and Boyden chamber assay. The results of Western blot, gelatin zymography and reversed transcription-PCR analysis showed that brazilein suppressed matrix metalloproteinase-2 (MMP-2) expression in a concentration-dependent manner. Brazilein also decreased the nuclear protein level of nuclear factor kappaB (NF-κB). Brazilein potently suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), phosphatidylinositide-3-kinase (PI3K) and Akt, but did not affect phosphorylation of extracellular signal regulating kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK). Additionally, treatment of SB203580 (p38 MAPK inhibitor) or wortmannin (PI3K inhibitor) resulted in a reduced activity and expression of MMP-2 as well as inhibition on cell migration and invasion in MDA-MB-231 cells. Taken together, these results suggest that brazilein inhibition of MDA-MB-231 cells may be mediated through inactivation of both PI3K/Akt and p38 MAPK signaling pathways, leading to inhibitory effect on NF-κB activation. Consequently, brazilein suppresses MMP-2 expression, and thus confers anti-migration and anti-invasion of MDA-MB-231 cells.
authors.affiliation: Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Chi-Ying
authors.initials: CY
authors.lastname: Hsieh
authors.forename: Pei-Chien
authors.initials: PC
authors.lastname: Tsai
authors.forename: Chiao-Lun
authors.initials: CL
authors.lastname: Chu
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
authors.forename: Long-Sen
authors.initials: LS
authors.lastname: Chang
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
authors.forename: Shinne-Ren
authors.initials: SR
authors.lastname: Lin
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D005260:Female; D006801:Humans; D007192:Indenes / Q000494:pharmacology*; D061965:Matrix Metalloproteinase Inhibitors / Q000494:pharmacology*; D015394:Molecular Structure; D016328:NF-kappa B / Q000737:chemistry / Q000378:metabolism; D016133:Polymerase Chain Reaction
chemical_list: D000970:Antineoplastic Agents; D001578:Benzopyrans; D007192:Indenes; D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; C050295:brazilein