Title:Role of Reactive Oxygen Species in Estrogen Dependant Breast Cancer Complication
Volume: 16
Issue: 2
Author(s): Ramesh Johar, Rohit Sharma, Amanpreet Kaur and Tapan K. Mukherjee
Affiliation:
Keywords:
Antioxidants, breast cancer, estrogens, prooxidants, reactive oxygen species (ROS), signaling.
Abstract: ROS have vital roles in cellular signaling and homeostasis. At low concentration, ROS promotes cancer
cell survival by the activation of growth factors and MAP-kinases (MAPKs) that further activates cell cycle
progression. At high concentration, ROS produces oxidative stress that activates programmed cell death or
apoptosis. However, this fine distinction of ROS action either as a growth promoter or pro-apoptotic agent
depends not only on dosage (concentration) but also on the duration, type, and site of ROS generation. The female
steroid estrogens and their various metabolites generate ROS in the breast cancer cells. Slow, sustained and
moderate level of ROS generated by estrogens and their metabolites cause initiation and progression of breast
cancer. ROS generated by estrogens affect pro-proliferative (e.g. cyclin D1, Cdc2), prosurvival (e.g. AKT),
antiapoptotic (e.g. BCl2) and pro-inflammatory (e.g. NF-κB) molecules. These multipronged actions of ROS lead
to the activation of several signaling pathways involved in the breast cancer cell survival and proliferation,
resulting in the progression of breast cancer. Present review article provides insights into the role of estrogen generated ROS and its
associated signaling pathways in the initiation and progression of breast cancer. The importance of ROS as breast cancer drug target has
also been discussed.