Inflammation

, Volume 34, Issue 3, pp 209–221

Sesamin Inhibits Macrophage-Induced Vascular Endothelial Growth Factor and Matrix Metalloproteinase-9 Expression and Proangiogenic Activity in Breast Cancer Cells

  • Chun-Chung Lee
  • Ko-Jiunn Liu
  • Yu-Chen Wu
  • Sue-Jane Lin
  • Ching-Chun Chang
  • Tze-Sing Huang
Article

DOI: 10.1007/s10753-010-9226-z

Cite this article as:
Lee, CC., Liu, KJ., Wu, YC. et al. Inflammation (2011) 34: 209. doi:10.1007/s10753-010-9226-z

Abstract

Sesamin is a sesame component with antihypertensive and antioxidative activities and has recently aroused much interest in studying its potential anticancer application. Macrophage is one of the infiltrating inflammatory cells in solid tumor and may promote tumor progression via enhancement of tumor angiogenesis. In this study, we investigated whether sesamin inhibited macrophage-enhanced proangiogenic activity of breast cancer cell lines MCF-7 and MDA-MB-231. Using vascular endothelial cell capillary tube and network formation assays, both breast cancer cell lines exhibited elevated proangiogenic activities after coculture with macrophages or pretreatment with macrophage-conditioned medium. This elevation of proangiogenic activity was drastically suppressed by sesamin. Vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) induced by macrophages in both cell lines were also inhibited by sesamin. Nuclear levels of HIF-1α and NF-κB, important transcription factors for VEGF and MMP-9 expression, respectively, were obviously reduced by sesamin. VEGF induction by macrophage in MCF-7 cells was shown to be via ERK, JNK, phosphatidylinositol 3-kinase, and NF-κB-mediated pathways. These signaling molecules and additional p38MAPK were also involved in macrophage-induced MMP-9 expression. Despite such diverse pathways were induced by macrophage, only Akt and p38MAPK activities were potently inhibited by sesamin. Expression of interleukin (IL)-6, IL-8, and tumor necrosis factor-α were substantially increased and involved in macrophage-induced VEGF and MMP-9 mRNA expression in MCF-7 cells. Sesamin effectively inhibited the expression of these cytokines to avoid the reinforced induction of VEGF and MMP-9. In conclusion, sesamin potently inhibited macrophage-enhanced proangiogenic activity of breast cancer cells via inhibition of VEGF and MMP-9 induction.

KEY WORDS

sesamin tumor-associated macrophage tumor angiogenesis Akt VEGF MMP-9 

ABBREVIATIONS

TAM

Tumor-associated macrophage

VEGF

Vascular endothelial growth factor

FGF

Fibroblast growth factor

IL

Interleukin

TNF-α

Tumor necrosis factor-α

TGF-β

Transforming growth factor-β

MMP

Matrix metalloproteinases

MϕCM

Macrophage-conditioned medium

MCFCM

MCF-7 cell-conditioned medium

MDACM

MDA-MB-231 cell-conditioned medium

PI3-K

Phosphatidylinositol 3-kinase

HUVECs

Human umbilical vein endothelial cells

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Chun-Chung Lee
    • 1
  • Ko-Jiunn Liu
    • 1
  • Yu-Chen Wu
    • 1
  • Sue-Jane Lin
    • 2
  • Ching-Chun Chang
    • 3
  • Tze-Sing Huang
    • 1
  1. 1.National Institute of Cancer Research, National Health Research InstitutesMiaoli CountyRepublic of China
  2. 2.Research Center for Emerging Viral Infections and Department of Medical Biotechnology and Laboratory Sciences, Chang Gung UniversityTao-YuanRepublic of China
  3. 3.Institute of BiotechnologyNational Cheng Kung UniversityTainanRepublic of China