Ferroptosis: An emerging therapeutic opportunity for cancer
Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
KeAi Communications Co., Ltd.
2022-03-01
|
| Series: | Genes and Diseases |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352304220301239 |
| _version_ | 1797725882937245696 |
|---|---|
| author | Liyuan Wang Xiaoguang Chen Chunhong Yan |
| author_facet | Liyuan Wang Xiaoguang Chen Chunhong Yan |
| author_sort | Liyuan Wang |
| collection | DOAJ |
| description | Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death, glutathione peroxidase 4 (GPX4) resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation, thereby suppressing ferroptosis. Indeed, RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in mice. Similarly, erastin and other system Xc− inhibitors can deplete intracellular glutathione required for GPX4 function, leading to lipid peroxidation and ferroptosis. As therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens, the agents capable of inducing ferroptosis hold great promises to improve current cancer therapy. This review will outline the molecular basis of ferroptosis, but focus on the strategies and the agents developed in recent years for therapeutic induction of ferroptosis. The potentials of these ferroptosis-inducing agents, which include system Xc− inhibitors, GPX4 inhibitors, and iron-based nanoparticles, in cancer therapy will be subsequently discussed. |
| first_indexed | 2024-03-12T10:37:42Z |
| format | Article |
| id | doaj.art-6a265331597b4a0f8e5b446222cf2254 |
| institution | Directory Open Access Journal |
| issn | 2352-3042 |
| language | English |
| last_indexed | 2024-03-12T10:37:42Z |
| publishDate | 2022-03-01 |
| publisher | KeAi Communications Co., Ltd. |
| record_format | Article |
| series | Genes and Diseases |
| spelling | doaj.art-6a265331597b4a0f8e5b446222cf22542023-09-02T08:33:51ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422022-03-0192334346Ferroptosis: An emerging therapeutic opportunity for cancerLiyuan Wang0Xiaoguang Chen1Chunhong Yan2Georgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Department of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, China; Department of Pharmacy, Peking University Third Hospital, Beijing 100191, ChinaDepartment of Pharmacology, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, ChinaGeorgia Cancer Center, Augusta University, Augusta, GA 30912, USA; Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University, Augusta, GA 30912, USA; Corresponding author. Georgia Cancer Center, 1410 Laney Walker Blvd., Augusta, GA 30912, USA.Ferroptosis, a new form of non-apoptotic, regulated cell death characterized by iron dependency and lipid peroxidation, is involved in many pathological conditions such as neurodegenerative diseases, heart ischemia/reperfusion injury, acute renal failure, and cancer. While metabolic dysfunctions can lead to excessive lipid peroxidation culminating in ferroptotic cell death, glutathione peroxidase 4 (GPX4) resides in the center of a network that functions to prevent lipid hydroperoxides from accumulation, thereby suppressing ferroptosis. Indeed, RSL3 and other small-molecule GPX4 inhibitors can induce ferroptosis in not only cultured cancer cells but also tumor xenografts implanted in mice. Similarly, erastin and other system Xc− inhibitors can deplete intracellular glutathione required for GPX4 function, leading to lipid peroxidation and ferroptosis. As therapy-resistant cancer cells are sensitive to GPX4-targeted therapeutic regimens, the agents capable of inducing ferroptosis hold great promises to improve current cancer therapy. This review will outline the molecular basis of ferroptosis, but focus on the strategies and the agents developed in recent years for therapeutic induction of ferroptosis. The potentials of these ferroptosis-inducing agents, which include system Xc− inhibitors, GPX4 inhibitors, and iron-based nanoparticles, in cancer therapy will be subsequently discussed.http://www.sciencedirect.com/science/article/pii/S2352304220301239Cancer therapyErastinFerroptosisGPX4Lipid peroxidationNanomedicine |
| spellingShingle | Liyuan Wang Xiaoguang Chen Chunhong Yan Ferroptosis: An emerging therapeutic opportunity for cancer Genes and Diseases Cancer therapy Erastin Ferroptosis GPX4 Lipid peroxidation Nanomedicine |
| title | Ferroptosis: An emerging therapeutic opportunity for cancer |
| title_full | Ferroptosis: An emerging therapeutic opportunity for cancer |
| title_fullStr | Ferroptosis: An emerging therapeutic opportunity for cancer |
| title_full_unstemmed | Ferroptosis: An emerging therapeutic opportunity for cancer |
| title_short | Ferroptosis: An emerging therapeutic opportunity for cancer |
| title_sort | ferroptosis an emerging therapeutic opportunity for cancer |
| topic | Cancer therapy Erastin Ferroptosis GPX4 Lipid peroxidation Nanomedicine |
| url | http://www.sciencedirect.com/science/article/pii/S2352304220301239 |
| work_keys_str_mv | AT liyuanwang ferroptosisanemergingtherapeuticopportunityforcancer AT xiaoguangchen ferroptosisanemergingtherapeuticopportunityforcancer AT chunhongyan ferroptosisanemergingtherapeuticopportunityforcancer |