Journal
PHYTOMEDICINE
Volume 22, Issue 4, Pages 462-468Publisher
ELSEVIER GMBH
DOI: 10.1016/j.phymed.2015.02.005
Keywords
Apoptosis; Breast cancer; Cell cycle; Microarray; Pharmacogenomics; Fabaceae
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Funding
- Special Fund of Forestry Industrial Research for Public Welfare of China [201004040]
- Importation of International Advanced Forestry Science and Technology, National Forestry Bureau [2012-4-06]
- Heilongjiang Province Science Foundation for Excellent Youths [JC200704]
- Project for Distinguished Teacher Abroad, Chinese Ministry of Education [MS2010DBLY031]
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Background: The low abundant cajanin stilbene acid (CSA) from Pigeon Pea (Cajanus cajan) has been shown to kill estrogen receptor alpha positive cancer cells in vitro and in vivo. Downstream effects such as cell cycle and apoptosis-related mechanisms have not been analyzed yet. Material and methods: We analyzed the activity of CSA by means of flow cytometry (cell cycle distribution, mitochondrial membrane potential, MMP), confocal laser scanning microscopy (MMP), DNA fragmentation assay (apoptosis), Western blotting (Bax and Bcl-2 expression, caspase-3 activation) as well as mRNA microarray hybridization and Ingenuity pathway analysis. Results: CSA induced G2/M arrest and apoptosis in a concentration dependent manner from 8.88 to 14.79 mu M. The MMP broke down, Bax was upregulated, Bcl-2 downregulated and caspase-3 activated. Microarray profiling revealed that CSA affected BRCA-related DNA damage response and cell cycle regulated chromosomal replication pathways. Conclusion: CSA inhibited breast cancer cells by DNA damage and cell cycle related signaling pathways leading to cell cycle arrest and apoptosis. (C) 2015 Elsevier GmbH. All rights reserved.
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