Tagitinin C induces ferroptosis through PERK-Nrf2-HO-1 signaling pathway in colorectal cancer cells
文献类型：期刊论文
| 作者 | Wei,Ruiran; Zhao,Yueqin; Wang,Juan; Yang,Xu; Li,Shunlin; Wang,Yinyuan; Yang,Xingzhi; Fei,Jimin; Hao,Xiaojiang ; Zhao,Yuhan
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| 刊名 | INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
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| 出版日期 | 2021 |
| 卷号 | 17期号:11页码:2703-2717 |
| ISSN号 | 1449-2288 |
| 关键词 | ferroptosis tagitinin C ROS ER stress Nrf2-HO-1 pathway ENDOPLASMIC-RETICULUM STRESS ER-STRESS OXIDATIVE STRESS TUMOR-SUPPRESSOR NRF2 DEATH IRON DIFFERENTIATION MECHANISMS RESISTANCE |
| DOI | 10.7150/ijbs.59404 |
| 英文摘要 | Rationale: Colorectal cancer (CRC) is a common malignant tumor of the digestive system. However, the efficacy of surgery and chemotherapy is limited. Ferroptosis is an iron-and reactive oxygen species (ROS)-dependent form of regulated cell death (RCD) and plays a vital role in tumor suppression. Ferroptosis inducing agents have been studied extensively as a novel promising way to fight against therapy resistant cancers. The aim of this study is to investigate the mechanism of action of tagitinin C (TC), a natural product, as a novel ferroptosis inducer in tumor suppression. Methods: The response of CRC cells to tagitinin C was assessed by cell viability assay, clonogenic assay, transwell migration assay, cell cycle assay and apoptosis assay. Molecular approaches including Western blot, RNA sequencing, quantitative real-time PCR and immunofluorescence were employed as well. Results: Tagitinin C, a sesquiterpene lactone isolated from Tithonia diversifolia, inhibits the growth of colorectal cancer cells including HCT116 cells, and induced an oxidative cellular microenvironment resulting in ferroptosis of HCT116 cells. Tagitinin C-induced ferroptosis was accompanied with the attenuation of glutathione (GSH) levels and increased in lipid peroxidation. Mechanistically, tagitinin C induced endoplasmic reticulum (ER) stress and oxidative stress, thus activating nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2). As a downstream gene (effector) of Nrf2, heme oxygenase-1 (HO-1) expression increased significantly with the treatment of tagitinin C. Upregulated HO-1 led to the increase in the labile iron pool, which promoted lipid peroxidation, meanwhile tagitinin C showed synergistic anti-tumor effect together with erastin. Conclusion: In summary, we provided the evidence that tagitinin C induces ferroptosis in colorectal cancer cells and has synergistic effect together with erastin. Mechanistically, tagitinin C induces ferroptosis through ER stress-mediated activation of PERK-Nrf2-HO-1 signaling pathway. Tagitinin C, identified as a novel ferroptosis inducer, may be effective chemosensitizer that can expand the efficacy and range of chemotherapeutic agents. |
| WOS记录号 | WOS:000678535400002 |
| 源URL | [http://ir.kib.ac.cn/handle/151853/73663]  |
| 专题 | 中国科学院昆明植物研究所 |
| 作者单位 | 1.Guizhou Med Univ, Ctr Tissue Engn & Stem Cell Res, Guiyang 550004, Peoples R China 2.Kunming Med Univ, Affiliated Hosp 3, Kunming 650118, Yunnan, Peoples R China 3.Kunming Med Univ, Yunnan Canc Hosp, Kunming 650118, Yunnan, Peoples R China 4.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resource West Chi, Kunming 650201, Yunnan, Peoples R China |
| 推荐引用方式 GB/T 7714 | Wei,Ruiran,Zhao,Yueqin,Wang,Juan,et al. Tagitinin C induces ferroptosis through PERK-Nrf2-HO-1 signaling pathway in colorectal cancer cells[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2021,17(11):2703-2717. |
| APA | Wei,Ruiran.,Zhao,Yueqin.,Wang,Juan.,Yang,Xu.,Li,Shunlin.,...&Ding,Xiao.(2021).Tagitinin C induces ferroptosis through PERK-Nrf2-HO-1 signaling pathway in colorectal cancer cells.INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,17(11),2703-2717. |
| MLA | Wei,Ruiran,et al."Tagitinin C induces ferroptosis through PERK-Nrf2-HO-1 signaling pathway in colorectal cancer cells".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 17.11(2021):2703-2717. |
入库方式： OAI收割
来源：昆明植物研究所
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