Targeting Nrf2- Keap1 signaling pathway for Cancer prevention. Farhad Jeddi1 , Mohammad Reza Sadeghi1, Narges Soozangar1, Farhad Pour Emamali2, ...
Targeting Nrf2- Keap1 signaling pathway for Cancer prevention Farhad Jeddi1 , Mohammad Reza Sadeghi1, Narges Soozangar1, Farhad Pour Emamali2, Nasser Samadi2
1. 2.
Student Research Committee, Tabriz University of Medical Sciences Department of Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Nrf2 protein is a transcription factor to regulate detoxifying enzymes and antioxidant. Nrf2 quickly modifies the sensitivity of the cell environment to electrophiles and oxidants by inducing the transcriptional activation of more than 100 detoxification and cytoprotective genes. In the cytosol, Keap1 chains Nrf2 by constantly targeting its degradation by ubiquitin ligase-dependent proteasome. Downstream genes of Nrf2 have the ability to inhibit damage to DNA, proteins, and lipids and contribute in the generation of new tissue. In normal conditions Nrf2 is anticancerous due to stimulation of detoxification and cytoprotective genes that keep cells from electrophilic/oxidative stress. These detoxification and cytoprotective genes that protect from cancer beginning however increase the resistance of tumor cells to chemotherapeutic agents, and in this situation Nrf2 is rapidly obtaining a protumoral characteristic. Some of the studies have proved a negative role for Nrf2 since it is upregulated in several drug-resistant tumors, and that blocking expression of Nrf2 within chemotherapy could be clinically useful. Therefore, the major goal of this paper is to identify the importance of Nrf2keap1 pathway in the prevention or promotion of cancer and its relation with chemoresistance.
