Palmitic acid-induced ferroptosis via CD36 activates ER stress to break calcium-iron balance in colon cancer cells,The FEBS Journal

当前位置： X-MOL 学术 › FEBS J. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Palmitic acid-induced ferroptosis via CD36 activates ER stress to break calcium-iron balance in colon cancer cells
The FEBS Journal ( IF 5.5 ) Pub Date : 2023-03-12 , DOI: 10.1111/febs.16772
Hao Kuang _{1,

2,

3,

4,

5} , Xuehua Sun _{1,

2,

3} , Ying Liu ₆ , Meng Tang _{1,

2,

3,

7} , Yan Wei _{1,

2,

3} , Yingying Shi _{1,

2,

3} , Ruibin Li _{1,

2,

3} , Guohui Xiao _{1,

2,

3} , Jinlin Kang _{1,

2,

3} , Fen Wang _{1,

2,

3} , Jin Peng _{1,

2,

3} , Hui Xu _{1,

2,

3} , Fuxiang Zhou _{1,

2,

3}

Affiliation

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.

中文翻译：

棕榈酸通过 CD36 诱导铁死亡，激活 ER 应激，破坏结肠癌细胞中的钙铁平衡

铁死亡以铁依赖性脂质过氧化为特征，是一种新型的程序性细胞死亡，在癌症治疗中可能具有巨大潜力。我们的研究发现，棕榈酸 (PA)在体外和体内均能抑制结肠癌细胞的活力，并伴有活性氧的积累和脂质过氧化。铁死亡抑制剂 Ferrostatin-1 而非 Z-VAD-FMK（一种泛半胱天冬酶抑制剂）、Necrostatin-1（一种有效的坏死性凋亡抑制剂）或 CQ（一种有效的自噬抑制剂）可以挽救 PA 诱导的细胞死亡表型。随后，我们证实，PA 通过过量的铁诱导铁死亡，因为细胞死亡被铁螯合剂去铁酮 (DFP) 抑制，而补充柠檬酸铁铵会加剧细胞死亡。从机制上讲，PA 通过诱导内质网 (ER) 应激导致 ER 钙释放并通过增加胞质钙水平调节转铁蛋白 (TF) 转运来影响细胞内铁含量。此外，我们观察到 CD36 高表达的细胞更容易受到 PA 诱导的铁死亡的影响。总而言之，我们的研究结果表明，PA 通过激活 ER 应激/ER 钙释放/TF 依赖性铁死亡来发挥抗癌特性，并且 PA 可能作为一种化合物来激活高 CD36 表达的结肠癌细胞中的铁死亡。

更新日期：2023-03-12

点击分享查看原文

点击收藏

阅读更多本刊新发论文