Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery
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 dose-dependent toxicity, high conc...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-02-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/3/349 |
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| author | Sepideh Mirzaei Ali Zarrabi Farid Hashemi Amirhossein Zabolian Hossein Saleki Negar Azami Soodeh Hamzehlou Mahdi Vasheghani Farahani Kiavash Hushmandi Milad Ashrafizadeh Haroon Khan Alan Prem Kumar |
| author_facet | Sepideh Mirzaei Ali Zarrabi Farid Hashemi Amirhossein Zabolian Hossein Saleki Negar Azami Soodeh Hamzehlou Mahdi Vasheghani Farahani Kiavash Hushmandi Milad Ashrafizadeh Haroon Khan Alan Prem Kumar |
| author_sort | Sepideh Mirzaei |
| collection | DOAJ |
| description | 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 dose-dependent 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. |
| first_indexed | 2024-03-09T00:30:27Z |
| format | Article |
| id | doaj.art-6714d735ec484db9a3df8e91128a8310 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T00:30:27Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-6714d735ec484db9a3df8e91128a83102023-12-11T18:32:56ZengMDPI AGAntioxidants2076-39212021-02-0110334910.3390/antiox10030349Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug DiscoverySepideh Mirzaei0Ali Zarrabi1Farid Hashemi2Amirhossein Zabolian3Hossein Saleki4Negar Azami5Soodeh Hamzehlou6Mahdi Vasheghani Farahani7Kiavash Hushmandi8Milad Ashrafizadeh9Haroon Khan10Alan Prem Kumar11Department of Biology, Faculty of Science, Islamic Azad University, Science and Research Branch, Tehran 1477893855, IranSabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla 34956, Istanbul, TurkeyDepartment of Comparative Biosciences, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417466191, IranYoung Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1477893855, IranYoung Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1477893855, IranYoung Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1477893855, IranYoung Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1477893855, IranYoung Researchers and Elite Club, Tehran Medical Sciences, Islamic Azad University, Tehran 1477893855, IranDepartment of Food Hygiene and Quality Control, Division of Epidemiology, Faculty of Veterinary Medicine, University of Tehran, Tehran 1417466191, IranSabanci University Nanotechnology Research and Application Center (SUNUM), Tuzla 34956, Istanbul, TurkeyDepartment of Pharmacy, Abdul Wali Khan University, Mardan 23200, PakistanCancer Science Institute of Singapore, Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117599, SingaporeDoxorubicin (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 dose-dependent 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.https://www.mdpi.com/2076-3921/10/3/349doxorubicinchemoresistanceoxidative stressredox signalingnuclear factor erythroid 2-related factor 2 (Nrf2)cancer therapy |
| spellingShingle | Sepideh Mirzaei Ali Zarrabi Farid Hashemi Amirhossein Zabolian Hossein Saleki Negar Azami Soodeh Hamzehlou Mahdi Vasheghani Farahani Kiavash Hushmandi Milad Ashrafizadeh Haroon Khan Alan Prem Kumar Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery Antioxidants doxorubicin chemoresistance oxidative stress redox signaling nuclear factor erythroid 2-related factor 2 (Nrf2) cancer therapy |
| title | Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery |
| title_full | Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery |
| title_fullStr | Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery |
| title_full_unstemmed | Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery |
| title_short | Nrf2 Signaling Pathway in Chemoprotection and Doxorubicin Resistance: Potential Application in Drug Discovery |
| title_sort | nrf2 signaling pathway in chemoprotection and doxorubicin resistance potential application in drug discovery |
| topic | doxorubicin chemoresistance oxidative stress redox signaling nuclear factor erythroid 2-related factor 2 (Nrf2) cancer therapy |
| url | https://www.mdpi.com/2076-3921/10/3/349 |
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