Cell cycle arrest and induction of apoptosis by cajanin stilbene acid from Cajanus cajan in breast cancer cells.
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.


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 µM. 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.


CONCLUSIONS
CSA inhibited breast cancer cells by DNA damage and cell cycle-related signaling pathways leading to cell cycle arrest and apoptosis.
Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin, China.
Yujie
Y
Fu
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Onat
O
Kadioglu
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany.
Benjamin
B
Wiench
Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin, China.
Zuofu
Z
Wei
Peking University People's Hospital, Beijing 100044, China.
Chang
C
Gao
Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin, China.
Meng
M
Luo
Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin, China.
Chengbo
C
Gu
Key Laboratory of Forest Plant Ecology, Ministry of Education, Northeast Forestry University, Harbin 150040, China; Engineering Research Center of Forest Bio-Preparation, Ministry of Education, Northeast Forestry University, Harbin, China.
Yuangang
Y
Zu
Department of Pharmaceutical Biology, Institute of Pharmacy and Biochemistry, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany. Electronic address: efferth@uni-mainz.de.
Thomas
T
Efferth
D017209:Apoptosis / Q000187:drug effects*; D036561:Cajanus / Q000737:chemistry; D053148:Caspase 3 / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D004249:DNA Damage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012459:Salicylates / Q000494:pharmacology*; D015398:Signal Transduction; D013267:Stilbenes / Q000494:pharmacology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C549543:3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid; C494826:BAX protein, human; C000595707:BCL2 protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D012459:Salicylates; D013267:Stilbenes; D051028:bcl-2-Associated X Protein; C505407:CASP3 protein, human; D053148:Caspase 3
Apoptosis; Breast cancer; Cell cycle; Fabaceae; Microarray; Pharmacogenomics