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Anti-Cancer Agents in Medicinal Chemistry


ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Role of Reactive Oxygen Species in Estrogen Dependant Breast Cancer Complication

Author(s): Ramesh Johar, Rohit Sharma, Amanpreet Kaur and Tapan K. Mukherjee

Volume 16, Issue 2, 2016

Page: [190 - 199] Pages: 10

DOI: 10.2174/1871520615666150518092315

Price: $65


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.

Keywords: Antioxidants, breast cancer, estrogens, prooxidants, reactive oxygen species (ROS), signaling.

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