Aglycone rich extracts of phytoestrogens cause ROS-mediated DNA damage in breast carcinoma cells.

Key Findings

Phytoestrogens are classified into: isoflavones, lignans, coumestans and stilbenes. They are shown to exert an anti-proliferative effect on various cancers in a number of in vitro and in vivo studies. This study demonstrated the role of reactive oxygen species (ROS) in causing potential cellular damage and in stimulating death selectively in cancer cells.  Soybean aglycone rich extracts (SARE) and flaxseed aglycone rich extracts (FSARE) were found to increase the ROS levels and modulate anti-oxidant enzymes within the cells, thereby disturbing the tightly regulated homeo-stasis of cancer cells and causing DNA damage. This supports an emerging model for cancer therapeutic by causing an imbalance in cellular homeostasis either by increasing ROS or suppressing anti-oxidants. In addition, future studies need to specifically target ROS sources, compare H2O2 generation and cause for differential radical scavenging enzymatic activity to enable an understanding of ROS-mediated novel therapeutics to selectively target cancer cells.

ABSTRACT

Phytoestrogens are known for their physiological role in lowering risk of osteoporosis, heart disease, breast cancer and menopausal symptoms. They are plant derived potent anti-oxidants, but tend to show pro-oxidant effect at higher concentrations. This study has been undertaken to exploit their pro-oxidant effect in the management of cancer. Cancer cells inherently possess high intracellular ROS levels, however, these levels do not cause harm to the cancer cells because of the anti-oxidant enzyme system. So, there is a need for a treatment strategy which could modulate the ROS levels. Breast cancer cell lines MCF-7 and MDA-MB-231 are treated with various concentrations of soyabean aglycone rich extracts (SARE) and flaxseed aglycone rich extracts (FSARE). The treatment brings about a significant decrease in super oxide dismutase (SOD) and glutathione peroxidase (GPx) activity, thereby leading to accumulation of superoxide ion and peroxide in the cells. The catalase (CAT) activity however, did not show a dose dependent change. The intra-cellular reactive oxygen species (ROS) levels increased and a marked change in mitochondrial membrane potential was detected. Cell cycle arrest was seen at S and G2/M phase in MCF-7 cells and high accumulation of cells in Sub G1 phase was seen in MDA-MB-231 cells. Microscopic evaluation indicated apoptotic morphology and DNA damage. This study suggests an important role of soyabean and flaxseed aglycones in modulating intracellular ROS in breast carcinoma.