RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer
Ferroptosis is an iron-dependent, oxidative cell death, and is characterized by iron-dependent accumulation of reactive oxygen species (ROS) within the cell. It has been implicated in various human diseases, including cancer. Recently, ferroptosis, as a non-apoptotic form of cell death, is emerging...
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Frontiers Media S.A.
2018-11-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2018.01371/full |
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| author | Xinbing Sui Xinbing Sui Xinbing Sui Ruonan Zhang Ruonan Zhang Ruonan Zhang Shuiping Liu Shuiping Liu Shuiping Liu Ting Duan Ting Duan Ting Duan Lijuan Zhai Lijuan Zhai Lijuan Zhai Mingming Zhang Mingming Zhang Mingming Zhang Xuemeng Han Xuemeng Han Xuemeng Han Yu Xiang Yu Xiang Yu Xiang Xingxing Huang Haoming Lin Tian Xie Tian Xie Tian Xie |
| author_facet | Xinbing Sui Xinbing Sui Xinbing Sui Ruonan Zhang Ruonan Zhang Ruonan Zhang Shuiping Liu Shuiping Liu Shuiping Liu Ting Duan Ting Duan Ting Duan Lijuan Zhai Lijuan Zhai Lijuan Zhai Mingming Zhang Mingming Zhang Mingming Zhang Xuemeng Han Xuemeng Han Xuemeng Han Yu Xiang Yu Xiang Yu Xiang Xingxing Huang Haoming Lin Tian Xie Tian Xie Tian Xie |
| author_sort | Xinbing Sui |
| collection | DOAJ |
| description | Ferroptosis is an iron-dependent, oxidative cell death, and is characterized by iron-dependent accumulation of reactive oxygen species (ROS) within the cell. It has been implicated in various human diseases, including cancer. Recently, ferroptosis, as a non-apoptotic form of cell death, is emerging in specific cancer types; however, its relevance in colorectal cancer (CRC) is unexplored and remains unclear. Here, we showed that ferroptosis inducer RSL3 initiated cell death and ROS accumulation in HCT116, LoVo, and HT29 CRC cells over a 24 h time course. Furthermore, we found that ROS levels and transferrin expression were elevated in CRC cells treated with RSL3 accompanied by a decrease in the expression of glutathione peroxidase 4 (GPX4), indicating an iron-dependent cell death, ferroptosis. Overexpression GPX4 resulted in decreased cell death after RSL3 treatment. Therefore, RSL3 was able to induce ferroptosis on three different CRC cell lines in vitro in a dose- and time-dependent manner, which was due to increased ROS and an increase in the cellular labile iron pool. Moreover, this effect was able to be reversed by overexpression of GPX4. Taken together, our results suggest that the induction of ferroptosis contributed to RSL3-induced cell death in CRC cells and ferroptosis may be a pervasive and dynamic form of cell death for cancer treatment. |
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| language | English |
| last_indexed | 2024-12-14T20:10:10Z |
| publishDate | 2018-11-01 |
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| spelling | doaj.art-fa31fb03e1f043809a8b3a16f3c5dd512022-12-21T22:48:57ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-11-01910.3389/fphar.2018.01371425764RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal CancerXinbing Sui0Xinbing Sui1Xinbing Sui2Ruonan Zhang3Ruonan Zhang4Ruonan Zhang5Shuiping Liu6Shuiping Liu7Shuiping Liu8Ting Duan9Ting Duan10Ting Duan11Lijuan Zhai12Lijuan Zhai13Lijuan Zhai14Mingming Zhang15Mingming Zhang16Mingming Zhang17Xuemeng Han18Xuemeng Han19Xuemeng Han20Yu Xiang21Yu Xiang22Yu Xiang23Xingxing Huang24Haoming Lin25Tian Xie26Tian Xie27Tian Xie28Department of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Hepatobiliary Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, ChinaDepartment of Medical Oncology, Holistic Integrative Oncology Institutes and Holistic Integrative Cancer Center of Traditional Chinese and Western Medicine, The Affiliated Hospital of Hangzhou Normal University, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaDepartment of Cancer Pharmacology, Holistic Integrative Pharmacy Institutes, College of Medicine, Hangzhou Normal University, Hangzhou, ChinaKey Laboratory of Elemene Class Anti-cancer Chinese Medicine of Zhejiang Province and Engineering Laboratory of Development and Application of Traditional Chinese Medicine from Zhejiang Province, Hangzhou Normal University, Hangzhou, ChinaFerroptosis is an iron-dependent, oxidative cell death, and is characterized by iron-dependent accumulation of reactive oxygen species (ROS) within the cell. It has been implicated in various human diseases, including cancer. Recently, ferroptosis, as a non-apoptotic form of cell death, is emerging in specific cancer types; however, its relevance in colorectal cancer (CRC) is unexplored and remains unclear. Here, we showed that ferroptosis inducer RSL3 initiated cell death and ROS accumulation in HCT116, LoVo, and HT29 CRC cells over a 24 h time course. Furthermore, we found that ROS levels and transferrin expression were elevated in CRC cells treated with RSL3 accompanied by a decrease in the expression of glutathione peroxidase 4 (GPX4), indicating an iron-dependent cell death, ferroptosis. Overexpression GPX4 resulted in decreased cell death after RSL3 treatment. Therefore, RSL3 was able to induce ferroptosis on three different CRC cell lines in vitro in a dose- and time-dependent manner, which was due to increased ROS and an increase in the cellular labile iron pool. Moreover, this effect was able to be reversed by overexpression of GPX4. Taken together, our results suggest that the induction of ferroptosis contributed to RSL3-induced cell death in CRC cells and ferroptosis may be a pervasive and dynamic form of cell death for cancer treatment.https://www.frontiersin.org/article/10.3389/fphar.2018.01371/fullRSL3ferroptosisglutathione peroxidase 4reactive oxygen speciescolorectal cancer |
| spellingShingle | Xinbing Sui Xinbing Sui Xinbing Sui Ruonan Zhang Ruonan Zhang Ruonan Zhang Shuiping Liu Shuiping Liu Shuiping Liu Ting Duan Ting Duan Ting Duan Lijuan Zhai Lijuan Zhai Lijuan Zhai Mingming Zhang Mingming Zhang Mingming Zhang Xuemeng Han Xuemeng Han Xuemeng Han Yu Xiang Yu Xiang Yu Xiang Xingxing Huang Haoming Lin Tian Xie Tian Xie Tian Xie RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer Frontiers in Pharmacology RSL3 ferroptosis glutathione peroxidase 4 reactive oxygen species colorectal cancer |
| title | RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer |
| title_full | RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer |
| title_fullStr | RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer |
| title_full_unstemmed | RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer |
| title_short | RSL3 Drives Ferroptosis Through GPX4 Inactivation and ROS Production in Colorectal Cancer |
| title_sort | rsl3 drives ferroptosis through gpx4 inactivation and ros production in colorectal cancer |
| topic | RSL3 ferroptosis glutathione peroxidase 4 reactive oxygen species colorectal cancer |
| url | https://www.frontiersin.org/article/10.3389/fphar.2018.01371/full |
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