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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.
AuthorsChi-Ying Hsieh, Pei-Chien Tsai, Chiao-Lun Chu, Fang-Rong Chang, Long-Sen Chang, Yang-Chang Wu, Shinne-Ren Lin
JournalChemico-biological interactions (Chem Biol Interact) Vol. 204 Issue 2 Pg. 105-15 (Jul 05 2013) ISSN: 1872-7786 [Electronic] Ireland
PMID23707804 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Chemical References
  • Antineoplastic Agents
  • Benzopyrans
  • Indenes
  • Matrix Metalloproteinase Inhibitors
  • NF-kappa B
  • brazilein
Topics
  • Antineoplastic Agents (pharmacology)
  • Benzopyrans (pharmacology)
  • Blotting, Western
  • Breast Neoplasms (drug therapy)
  • Cell Line, Tumor
  • Cell Movement (drug effects)
  • Female
  • Humans
  • Indenes (pharmacology)
  • Matrix Metalloproteinase Inhibitors (pharmacology)
  • Molecular Structure
  • NF-kappa B (chemistry, metabolism)
  • Polymerase Chain Reaction

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