Nrf2 signaling pathway in cisplatin chemotherapy: potential involvement in organ protection and chemoresistance

Mirzaei, Sepideh and Mohammadi, Aliasghar Tabatabaei and Gholami, Mohammad Hossein and Hashemi, Farid and Zarrabi, Ali and Zabolian, Amirhossein and Hushmandi, Kiavash and Makvandi, Pooyan and Samec, Marek and Liskova, Alena and Kubatka, Peter and Nabavi, Noushin and Aref, Amir Reza and Ashrafizadeh, Milad and Khan, Haroon and Najafi, Masoud (2021) Nrf2 signaling pathway in cisplatin chemotherapy: potential involvement in organ protection and chemoresistance. Pharmacological Research, 167 . ISSN 1043-6618 (Print) 1096-1186 (Online)

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Nuclear factor erythroid 2-related factor 2 (Nrf2) is a vital transcription factor and its induction is of significant importance for protecting against oxidative damage. Increased levels of Reactive Oxygen Species (ROS) stimulate Nrf2 signaling, enhancing the activity of antioxidant enzymes such as catalase, superoxide dismutase and glutathione peroxidase. These enzymes are associated with retarding oxidative stress. On the other hand, Nrf2 activation in cancer cells is responsible for the development of chemoresistance due to disrupting oxidative mediated-cell death by reducing ROS levels. Cisplatin (CP), cis-diamminedichloroplatinum(II), is a potent anti-tumor agent extensively used in cancer therapy, but its frequent application leads to the development of chemoresistance as well. In the present study, association of Nrf2 signaling with chemoresistance to CP and protection against its deleterious effects is discussed. Anti-tumor compounds, mainly phytochemicals, retard chemoresistance by suppressing Nrf2 signaling. Upstream mediators such as microRNAs can regulate Nrf2 expression during CP chemotherapy regimens. Protection against side effects of CP is mediated via activating Nrf2 signaling and its downstream targets activating antioxidant defense system. Protective agents that activate Nrf2 signaling, can ameliorate CP-mediated ototoxicity, nephrotoxicity and neurotoxicity. Reducing ROS levels and preventing cell death are the most important factors involved in alleviating CP toxicity upon Nrf2 activation. As pre-clinical experiments advocate the role of Nrf2 in chemoprotection and CP resistance, translating these findings to the clinic can provide a significant progress in treatment of cancer patients.
Item Type: Article
Uncontrolled Keywords: Chemoprotection; Chemoresistance; Cisplatin; Nrf2; Oxidative stress; ROS
Divisions: Faculty of Engineering and Natural Sciences
Sabancı University Nanotechnology Research and Application Center
Depositing User: Ali Zarrabi
Date Deposited: 03 Sep 2022 17:17
Last Modified: 03 Sep 2022 17:17

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