Palmitic acid-induced ferroptosis via CD36 activates ER stress to break calcium-iron balance in colon cancer cells
© 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies..
Ferroptosis, featuring an iron-dependent peroxidation of lipids, is a novel form of programmed cell death that may hold great potential in cancer therapy. Our study found that palmitic acid (PA) inhibited colon cancer cell viability in vitro and in vivo, in conjunction with an accumulation of reactive oxygen species and lipid peroxidation. The ferroptosis inhibitor Ferrostatin-1 but not Z-VAD-FMK (a pan-caspase inhibitor), Necrostatin-1 (a potent necroptosis inhibitor), or CQ (a potent inhibitor of autophagy), rescued the cell death phenotype induced by PA. Subsequently, we verified that PA induces ferroptotic cell death through excess iron as cell death was inhibited by iron chelator deferiprone (DFP), while it was exacerbated by a supplement of ferric ammonium citrate. Mechanistically, PA affects intracellular iron content by inducing endoplasmic reticulum (ER) stress leading to ER calcium release and regulating transferrin (TF) transport through increasing cytosolic calcium levels. Furthermore, we observed that cells with high expression of CD36 were more vulnerable to PA-induced ferroptosis. Altogether, our findings reveal that PA engages in anti-cancer properties by activating ER stress/ER calcium release/TF-dependent ferroptosis, and PA might serve as a compound to activate ferroptosis in colon cancer cells with high CD36 expression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:290 |
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| Enthalten in: |
The FEBS journal - 290(2023), 14 vom: 12. Juli, Seite 3664-3687 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Kuang, Hao [VerfasserIn] |
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| Links: |
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| Themen: |
2V16EO95H1 |
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| Anmerkungen: |
Date Completed 21.07.2023 Date Revised 21.07.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/febs.16772 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM354125427 |
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| 520 | |a © 2023 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies. | ||
| 520 | |a Ferroptosis, featuring an iron-dependent peroxidation of lipids, is a novel form of programmed cell death that may hold great potential in cancer therapy. Our study found that palmitic acid (PA) inhibited colon cancer cell viability in vitro and in vivo, in conjunction with an accumulation of reactive oxygen species and lipid peroxidation. The ferroptosis inhibitor Ferrostatin-1 but not Z-VAD-FMK (a pan-caspase inhibitor), Necrostatin-1 (a potent necroptosis inhibitor), or CQ (a potent inhibitor of autophagy), rescued the cell death phenotype induced by PA. Subsequently, we verified that PA induces ferroptotic cell death through excess iron as cell death was inhibited by iron chelator deferiprone (DFP), while it was exacerbated by a supplement of ferric ammonium citrate. Mechanistically, PA affects intracellular iron content by inducing endoplasmic reticulum (ER) stress leading to ER calcium release and regulating transferrin (TF) transport through increasing cytosolic calcium levels. Furthermore, we observed that cells with high expression of CD36 were more vulnerable to PA-induced ferroptosis. Altogether, our findings reveal that PA engages in anti-cancer properties by activating ER stress/ER calcium release/TF-dependent ferroptosis, and PA might serve as a compound to activate ferroptosis in colon cancer cells with high CD36 expression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CD36 | |
| 650 | 4 | |a ER stress | |
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| 700 | 1 | |a Sun, Xuehua |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Ying |e verfasserin |4 aut | |
| 700 | 1 | |a Tang, Meng |e verfasserin |4 aut | |
| 700 | 1 | |a Wei, Yan |e verfasserin |4 aut | |
| 700 | 1 | |a Shi, Yingying |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Ruibin |e verfasserin |4 aut | |
| 700 | 1 | |a Xiao, Guohui |e verfasserin |4 aut | |
| 700 | 1 | |a Kang, Jinlin |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Fen |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Hui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Fuxiang |e verfasserin |4 aut | |
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