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

Abstract

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, 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.

CONCLUSION:

CSA inhibited breast cancer cells by DNA damage and cell cycle-related signaling pathways leading to cell cycle arrest and apoptosis.

• Authors: Yujie Fu, Onat Kadioglu, Benjamin Wiench, Zuofu Wei, Chang Gao, Meng Luo, Chengbo Gu, Yuangang Zu, Thomas Efferth
• Journal: Phytomedicine : international journal of phytotherapy and phytopharmacology (Phytomedicine) Vol. 22 Issue 4 Pg. 462-8 (Apr 15 2015) ISSN: 1618-095X [Electronic] Germany
• PMID: 25925968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier GmbH. All rights reserved.

Chemical References

• 3-hydroxy-4-prenyl-5-methoxystilbene-2-carboxylic acid
• BAX protein, human
• BCL2 protein, human
• Proto-Oncogene Proteins c-bcl-2
• Salicylates
• Stilbenes
• bcl-2-Associated X Protein
• CASP3 protein, human
• Caspase 3

Topics

• Apoptosis (drug effects)
• Cajanus (chemistry)
• Caspase 3 (metabolism)
• Cell Cycle Checkpoints (drug effects)
• DNA Damage
• Gene Expression Regulation, Neoplastic
• Humans
• MCF-7 Cells
• Membrane Potential, Mitochondrial (drug effects)
• Proto-Oncogene Proteins c-bcl-2 (metabolism)
• Salicylates (pharmacology)
• Signal Transduction
• Stilbenes (pharmacology)
• bcl-2-Associated X Protein (metabolism)