Ultrasmall iron oxide nanoparticles induced ferroptosis via Beclin1/ATG5-dependent autophagy pathway

Wen, Jianbo; Chen, Hanren; Ren, Zhijun; Zhang, Peng; Chen, Jianjiao; Jiang, Shu-Lian

doi:10.1186/s40580-021-00260-z

“…The curcumin analogues ALZ003 and quinkalim can lead to ferroptosis in glioma cells, thus opening new avenues for the treatment of temozolomide (TMZ)-resistant glioblastoma ( 30 , 31 ). Iron oxide nanoparticles are safe and effective ferroptosis and apoptosis inducers and can be used as a combination therapy for glioblastoma ( 32 , 33 ).…”

Section: Introductionmentioning

confidence: 99%

LncRNA PELATON, a Ferroptosis Suppressor and Prognositic Signature for GBM

Fu

¹

,

Zhang

²

,

Li

³

et al. 2022

View full text Add to dashboard Cite

PELATON is a long noncoding RNA also known as long intergenic nonprotein coding RNA 1272 (LINC01272). The known reports showed that PELATON functions as an onco-lncRNA or a suppressor lncRNA by suppressing miRNA in colorectal cancer, gastric cancer and lung cancer. In this study, we first found that PELATON, as an onco-lncRNA, alleviates the ferroptosis driven by mutant p53 and promotes mutant p53-mediated GBM proliferation. We also first confirmed that PELATON is a new ferroptosis suppressor lncRNA that functions as a ferroptosis inhibitor mainly by mutant P53 mediating the ROS ferroptosis pathway, which inhibits the production of ROS, reduces the levels of divalent iron ions, promotes the expression of SLC7A11, and inhibits the expression of ACSL4 and COX2.PELATON can inhibit the expression of p53 in p53 wild-type GBM cells and regulate the expression of BACH1 and CD44, but it has no effect on p53, BACH1 and CD44 in p53 mutant GBM cells. PELATON and p53 can form a complex through the RNA binding protein EIF4A3. Knockdown of PELATON resulted in smaller mitochondria, increased mitochondrial membrane density, and enhanced sensitivity to ferroptosis inducers to inhibit GBM cell proliferation and invasion. In addition, we established a favourite prognostic model with NCOA4 and PELATON. PELATON is a promising target for the prognosis and treatment of GBM.

show abstract

“…Therefore, we hypothesized that these factors might have different targets for suppressing the same mode of death. It has been established that certain drugs can induce ferroptosis in tumor cells by activating autophagy [ 42 ]. To determine whether Rh4 can also induce ferroptosis in CRC cells by activating autophagy, we pretreated HT29 and HCT116 cells with 3-MA and then treated the cells with Rh4.…”

Section: Resultsmentioning

confidence: 99%

Ginsenoside Rh4 Inhibits Colorectal Cancer Cell Proliferation by Inducing Ferroptosis via Autophagy Activation

Wu

¹

,

Pi

²

,

Chen

³

et al. 2022

Evidence-Based Complementary and Alternative Medicine

View full text Add to dashboard Cite

Colorectal cancer (CRC) is a severe threat to human health. Ginsenosides such as ginsenoside Rh4 have been widely studied in the antitumor field. Here, we investigated the antiproliferative activity and mechanism of Rh4 against CRC in vivo and in vitro. The CRC xenograft model showed that Rh4 inhibited xenograft tumor growth with few side effects ( p < 0.05 ). As determined by MTT colorimetric assays, Western blotting, and immunohistochemical analysis, Rh4 effectively inhibited CRC cell proliferation through autophagy and ferroptosis ( p < 0.05 ). Rh4 significantly upregulated autophagy and ferroptosis marker expression in CRC cells and xenograft tumor tissues in the present study ( p < 0.05 ). Interestingly, the ferroptosis inhibitor ferrostatin-1 (Fer-1) reversed Rh4-induced ferroptosis ( p < 0.05 ). Moreover, the autophagy inhibitor 3-methyladenine (3-MA) also reversed Rh4-induced ferroptosis ( p < 0.05 ). These results indicate that Rh4-induced ferroptosis is regulated via the autophagy pathway. In addition, Rh4 increased reactive oxygen species (ROS) accumulation, leading to the activation of the ROS/p53 signaling pathway ( p < 0.05 ). Transcriptome sequencing also confirmed this ( p < 0.05 ). Moreover, the ROS scavenger N-acetyl-cysteine (NAC) reversed the inhibitory effect of Rh4 on CRC cells ( p < 0.05 ). Therefore, this study proves that Rh4 inhibits cancer cell proliferation by activating the ROS/p53 signaling pathway and activating autophagy to induce ferroptosis, which provides necessary scientific evidence of the great anticancer potential of Rh4.

show abstract

“…Furthermore, we previously observed that AgNPs selectively eliminate certain TNBCs, ovarian cancer cells, and NCSLC with a mesenchymal phenotype [23,27,29,33]. Reports indicate that certain nanoparticles, including iron-core nanoparticles [70,71], titanium dioxide (TiO2) [72], ultrasmall poly (ethylene glycol)-coated silica nanoparticles [73], cobalt NPs [74], and manganese silicate nanobubbles [75], induce lipid oxidation in a variety of cell types. The cause of the general vulnerability of various cancers with an EMT phenotype to engineered nanomaterials has not been firmly established, but our data indicate that nanoparticle-induced lipid peroxidation and proteotoxicity may play a key role in this.…”

Section: Discussionmentioning

confidence: 99%

Low Doses of Silver Nanoparticles Selectively Induce Lipid Peroxidation and Proteotoxic Stress in Mesenchymal Subtypes of Triple-Negative Breast Cancer

Snyder

¹

,

Rohde

²

,

Fahrenholtz

³

et al. 2021

Cancers

View full text Add to dashboard Cite

Molecular profiling of tumors shows that triple-negative breast cancer (TNBC) can be stratified into mesenchymal (claudin-low breast cancer; CLBC) and epithelial subtypes (basal-like breast cancer; BLBC). Subtypes differ in underlying genetics and in response to therapeutics. Several reports indicate that therapeutic strategies that induce lipid peroxidation or proteotoxicity may be particularly effective for various cancers with a mesenchymal phenotype such as CLBC, for which no specific treatment regimens exist and outcomes are poor. We hypothesized that silver nanoparticles (AgNPs) can induce proteotoxic stress and cause lipid peroxidation to a greater extent in CLBC than in BLBC. We found that AgNPs were lethal to CLBCs at doses that had little effect on BLBCs and were non-toxic to normal breast epithelial cells. Analysis of mRNA profiles indicated that sensitivity to AgNPs correlated with expression of multiple CLBC-associated genes. There was no correlation between sensitivity to AgNPs and sensitivity to silver cations, uptake of AgNPs, or proliferation rate, indicating that there are other molecular factors driving sensitivity to AgNPs. Mechanistically, we found that the differences in sensitivity of CLBC and BLBC cells to AgNPs were driven by peroxidation of lipids, protein oxidation and aggregation, and subsequent proteotoxic stress and apoptotic signaling, which were induced in AgNP-treated CLBC cells, but not in BLBC cells. This study shows AgNPs are a specific treatment for CLBC and indicates that stratification of TNBC subtypes may lead to improved outcomes for other therapeutics with similar mechanisms of action.

show abstract

Ultrasmall iron oxide nanoparticles induced ferroptosis via Beclin1/ATG5-dependent autophagy pathway

Cited by 50 publications

References 32 publications

LncRNA PELATON, a Ferroptosis Suppressor and Prognositic Signature for GBM

LncRNA PELATON, a Ferroptosis Suppressor and Prognositic Signature for GBM

Ginsenoside Rh4 Inhibits Colorectal Cancer Cell Proliferation by Inducing Ferroptosis via Autophagy Activation

Low Doses of Silver Nanoparticles Selectively Induce Lipid Peroxidation and Proteotoxic Stress in Mesenchymal Subtypes of Triple-Negative Breast Cancer

Contact Info

Product

Resources

About