Cell cycle arrest and induction of apoptosis by cajanin stilbene acid from Cajanus cajan in breast cancer cells, Phytomedicine, 11 March 2015, Yujie Fua, b, 1, Onat Kadiogluc, 1, Benjamin Wienchc, Zuofu Weia, b, Chang Gaod, Meng Luoa, b, Xiaohe Yange, Chengbo Gua, b, Yuangang Zua, b, Thomas Efferth
Cell cycle arrest and induction of apoptosis by cajanin stilbene acid from Cajanus cajan in breast cancer cells
- Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China
- b Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin, China
- c Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany
- d Peking University People’s Hospital, Beijing 100044, China
- e Julius L. Chambers Biomedical/Biotechnology Research Institute, North Carolina Central University, North Carolina Research Campus, Kannapolis, NC 28081, USA
Background: The low abundant cajanin stilbene acid (CSA) from Pigeon Pea (Cajanus cajan) has been shown to kill estrogen receptor α 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, capsase-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 µM. The MMP broke down, Bax was upregulated, Bcl-2 downregulated and capase-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.