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Published on: August 27, 2013
Role of Endothelin 1 on Proliferation and Migration of Human MCF-7 Cells
Irfan Cinar1, Muhammed Yayla1, Muhammet Celik2
1Department of Pharmacology, Kastamonu University School of Medicine, Kastamonu, Turkey.
Objective:
The aim of this study was to explore the role of endothelin 1 (ET-1) in human breast cancer proliferation and migration and antagonism of endothelin receptor A (ETAR) and endothelin receptor B (ETBR) by using the non-selective dual ETA/ETB receptor antagonist bosentan and determine its anti-proliferative, anti-metastatic, and apoptotic effects demonstrated by nuclear factor kappa B (NF-kB), vascular endothelial growth factor (VEGF), Caspase 3 and Caspase 9 expression on endothelin-induced proliferation of MCF-7 cell line in vitro.
Materials And Methods:
A total of 8,000 cells were seeded into e-plates 24 hours after the cells were incubated with or without 10-4 M BOS (1 hour before ET-1 treatment); 10-7, 10-8, and 10-9 M ET-1 for 1-4 days.
Results:
Whether ET-1 is present or not in the tumor area, bosentan exerts anti-proliferative effect on breast cancer. However, ET-1 and bosentan group showed important inhibitory effect on tumor migration compared to bosentan alone, which can be attributed to increased activity of ET-1 axis in the presence of ET-1. The imbalance among the NF-kB, caspases, and VEGF, which are predictive factors of carcinogenesis significantly improved after bosentan administration.
Conclusion:
Our study definitely demonstrated ET-1 and its critical role in cancer progression with apoptotic and anti-apoptotic pathways (NF-κB) and VEGF expression, and migration analyses were also performed. The second major finding was that bosentan inhibited ET-1-mediated effects on tumor proliferation and migration.
Insights
Endothelin 1 (ET-1) drives breast cancer growth and migration. Bosentan, an endothelin receptor antagonist, inhibits ET-1
Area of Science:
- Molecular Oncology
- Cancer Biology
- Pharmacology
Background:
- Endothelin 1 (ET-1) is implicated in human breast cancer progression.
- Endothelin receptors A (ETAR) and B (ETBR) are potential therapeutic targets.
- Understanding ET-1's role in proliferation and migration is crucial for novel treatment strategies.
Purpose of the Study:
- To investigate the role of ET-1 in human breast cancer cell proliferation and migration.
- To evaluate the anti-proliferative, anti-metastatic, and apoptotic effects of bosentan, a dual ETAR/ETBR antagonist.
- To analyze the impact of bosentan on nuclear factor kappa B (NF-kB), vascular endothelial growth factor (VEGF), Caspase 3, and Caspase 9 expression.
Main Methods:
- MCF-7 breast cancer cells were treated with varying concentrations of ET-1 and bosentan (BOS) in vitro.
- Cell proliferation and migration were assessed.
- Expression levels of NF-kB, VEGF, Caspase 3, and Caspase 9 were analyzed.
Main Results:
- Bosentan demonstrated an anti-proliferative effect on breast cancer cells, regardless of ET-1 presence.
- The combination of ET-1 and bosentan significantly inhibited tumor migration compared to bosentan alone.
- Bosentan administration improved the balance of NF-kB, caspases, and VEGF, key factors in carcinogenesis.
Conclusions:
- ET-1 plays a critical role in breast cancer progression via apoptotic and anti-apoptotic pathways (NF-kB) and VEGF.
- Bosentan effectively inhibited ET-1-mediated tumor proliferation and migration.
- These findings highlight the therapeutic potential of endothelin receptor antagonists in breast cancer treatment.
