The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway
Ferroptosis represents a typical process that has dual functions in cell fate decisions since the reduction and/or inhibition of ferroptosis is desirable for the therapies of diseases such as neurological disorders, localized ischemia-reperfusion, kidney injury, and hematological diseases, while the...
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MDPI AG
2022-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/19/11004 |
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| author | Dóra Varga Péter Hajdinák Kinga Makk-Merczel András Szarka |
| author_facet | Dóra Varga Péter Hajdinák Kinga Makk-Merczel András Szarka |
| author_sort | Dóra Varga |
| collection | DOAJ |
| description | Ferroptosis represents a typical process that has dual functions in cell fate decisions since the reduction and/or inhibition of ferroptosis is desirable for the therapies of diseases such as neurological disorders, localized ischemia-reperfusion, kidney injury, and hematological diseases, while the enhanced ferroptosis of cancer cells may benefit patients with cancer. The JNK pathway also has a real dual function in the fate of cells. Multiple factors suggest a potential link between the ferroptotic and JNK pathways; (i) both processes are ROS mediated; (ii) both can be inhibited by lipid peroxide scavengers; (iii) RAS mutations may play a role in the initiation of both pathways. We aimed to investigate the possible link between ferroptosis and the JNK pathway. Interestingly, JNK inhibitor co-treatment could enhance the cancer cytotoxic effect of the ferroptosis inducers in NRAS and KRAS mutation-harboring cells (HT-1080 and MIA PaCa-2). Since cancer’s cytotoxic effect from the JNK inhibitors could only be suspended by the ferroptosis inhibitors, and that sole JNK-inhibitor treatment did not affect cell viability, it seems that the JNK inhibitors “just” amplify the effect of the ferroptosis inducers. This cancer cell death amplifying effect of the JNK inhibitors could not be observed in other oxidative stress-driven cell deaths. Hence, it seems it is specific to ferroptosis. Finally, our results suggest that GSH content/depletion could be an important candidate for switching the anti-cancer effect of JNK inhibitors. |
| first_indexed | 2024-03-09T21:43:07Z |
| format | Article |
| id | doaj.art-76d44457990749c7a4ca79a72c7eb004 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:43:07Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-76d44457990749c7a4ca79a72c7eb0042023-11-23T20:25:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-09-0123191100410.3390/ijms231911004The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK PathwayDóra Varga0Péter Hajdinák1Kinga Makk-Merczel2András Szarka3Laboratory of Biochemistry and Molecular Biology, Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Szent Gellért tér 4, H-1111 Budapest, HungaryLaboratory of Biochemistry and Molecular Biology, Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Szent Gellért tér 4, H-1111 Budapest, HungaryLaboratory of Biochemistry and Molecular Biology, Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Szent Gellért tér 4, H-1111 Budapest, HungaryLaboratory of Biochemistry and Molecular Biology, Department of Applied Biotechnology and Food Science, Budapest University of Technology and Economics, Szent Gellért tér 4, H-1111 Budapest, HungaryFerroptosis represents a typical process that has dual functions in cell fate decisions since the reduction and/or inhibition of ferroptosis is desirable for the therapies of diseases such as neurological disorders, localized ischemia-reperfusion, kidney injury, and hematological diseases, while the enhanced ferroptosis of cancer cells may benefit patients with cancer. The JNK pathway also has a real dual function in the fate of cells. Multiple factors suggest a potential link between the ferroptotic and JNK pathways; (i) both processes are ROS mediated; (ii) both can be inhibited by lipid peroxide scavengers; (iii) RAS mutations may play a role in the initiation of both pathways. We aimed to investigate the possible link between ferroptosis and the JNK pathway. Interestingly, JNK inhibitor co-treatment could enhance the cancer cytotoxic effect of the ferroptosis inducers in NRAS and KRAS mutation-harboring cells (HT-1080 and MIA PaCa-2). Since cancer’s cytotoxic effect from the JNK inhibitors could only be suspended by the ferroptosis inhibitors, and that sole JNK-inhibitor treatment did not affect cell viability, it seems that the JNK inhibitors “just” amplify the effect of the ferroptosis inducers. This cancer cell death amplifying effect of the JNK inhibitors could not be observed in other oxidative stress-driven cell deaths. Hence, it seems it is specific to ferroptosis. Finally, our results suggest that GSH content/depletion could be an important candidate for switching the anti-cancer effect of JNK inhibitors.https://www.mdpi.com/1422-0067/23/19/11004ferroptosisJNK pathwayreactive oxygen speciescell deathcancer |
| spellingShingle | Dóra Varga Péter Hajdinák Kinga Makk-Merczel András Szarka The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway International Journal of Molecular Sciences ferroptosis JNK pathway reactive oxygen species cell death cancer |
| title | The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway |
| title_full | The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway |
| title_fullStr | The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway |
| title_full_unstemmed | The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway |
| title_short | The Possible Connection of Two Dual Function Processes: The Relationship of Ferroptosis and the JNK Pathway |
| title_sort | possible connection of two dual function processes the relationship of ferroptosis and the jnk pathway |
| topic | ferroptosis JNK pathway reactive oxygen species cell death cancer |
| url | https://www.mdpi.com/1422-0067/23/19/11004 |
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