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Title: Nrf2 signaling pathway in chemoprotection and doxorubicin resistance: potential application in drug discovery
Authors: Mirzaei, Sepideh
Zarrabi, Ali
Hashemi, Farid
Zabolian, Amirhossein
Saleki, Hossein
Azami, Negar
Hamzehlou, Soodeh
Farahani, Mahdi Vasheghani
Hushmandi, Kiavash
Ashrafizadeh, Milad
Khan, Haroon
Kumar, Alan Prem 
Keywords: Chemoresistance
Nuclear factor erythroid 2?related factor 2 (Nrf2), cancer therapy
Oxidative stress
Redox signaling
Issue Date: 26-Feb-2021
Publisher: MDPI
Citation: Mirzaei, Sepideh, Zarrabi, Ali, Hashemi, Farid, Zabolian, Amirhossein, Saleki, Hossein, Azami, Negar, Hamzehlou, Soodeh, Farahani, Mahdi Vasheghani, Hushmandi, Kiavash, Ashrafizadeh, Milad, Khan, Haroon, Kumar, Alan Prem (2021-02-26). Nrf2 signaling pathway in chemoprotection and doxorubicin resistance: potential application in drug discovery. Antioxidants 10 (3) : Jan-27. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: Doxorubicin (DOX) is extensively applied in cancer therapy due to its efficacy in suppressing cancer progression and inducing apoptosis. After its discovery, this chemotherapeutic agent has been frequently used for cancer therapy, leading to chemoresistance. Due to dosedependent toxicity, high concentrations of DOX cannot be administered to cancer patients. Therefore, experiments have been directed towards revealing underlying mechanisms responsible for DOX resistance and ameliorating its adverse effects. Nuclear factor erythroid 2?related factor 2 (Nrf2) signaling is activated to increase levels of reactive oxygen species (ROS) in cells to protect them against oxidative stress. It has been reported that Nrf2 activation is associated with drug resistance. In cells exposed to DOX, stimulation of Nrf2 signaling protects cells against cell death. Various upstream mediators regulate Nrf2 in DOX resistance. Strategies, both pharmacological and genetic interventions, have been applied for reversing DOX resistance. However, Nrf2 induction is of importance for alleviating side effects of DOX. Pharmacological agents with naturally occurring compounds as the most common have been used for inducing Nrf2 signaling in DOX amelioration. Furthermore, signaling networks in which Nrf2 is a key player for protection against DOX adverse effects have been revealed and are discussed in the current review. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Source Title: Antioxidants
ISSN: 2076-3921
DOI: 10.3390/antiox10030349
Rights: Attribution 4.0 International
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