Nrf2 signaling pathway in chemoprotection and doxorubicin resistance: potential application in drug discovery

Mirzaei, Sepideh and Zarrabi, Ali and Hashemi, Farid and Zabolian, Amirhossein and Saleki, Hossein and Azami, Negar and Hamzehlou, Soodeh and Farahani, Mahdi Vasheghani and Hushmandi, Kiavash and Ashrafizadeh, Milad and Khan, Haroon and Kumar, Alan Prem (2021) Nrf2 signaling pathway in chemoprotection and doxorubicin resistance: potential application in drug discovery. Antioxidants, 10 (3). ISSN 2076-3921

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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.
Item Type: Article
Uncontrolled Keywords: Chemoresistance; Doxorubicin; Nuclear factor erythroid 2‐related factor 2 (Nrf2), cancer therapy; Oxidative stress; Redox signaling
Divisions: Faculty of Engineering and Natural Sciences
Sabancı University Nanotechnology Research and Application Center
Depositing User: Ali Zarrabi
Date Deposited: 31 Aug 2022 15:16
Last Modified: 31 Aug 2022 15:16

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