Vitamin C induces ferroptosis in anaplastic thyroid cancer cells by ferritinophagy activation

Wang, Xiaowen; Xu, Sheng; Zhang, Li; Cheng, Xian; Yu, Huixin; Bao, Jiandong; Lu, Rongrong

doi:10.1016/j.bbrc.2021.02.126

Cited by 54 publications

(52 citation statements)

References 21 publications

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“…P53, as an upstream mediator of SLC7A11, mediates the repression of SLC7A11 to initiate ferroptosis in tumour cells [11]. In addition to breast cancer, colorectal cancer, and anaplastic thyroid cancer [12][13][14], ferroptosis also exerts anticancer effects in OS [15,16]. Some clinical drugs including sulfasalazine and sorafenib have proven to induce ferroptosis to trigger anticancer effects [17], via inhibiting the system Xc - [18,19].…”

Section: Introductionmentioning

confidence: 99%

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Luo

Gao

Zou

et al. 2021

Oxidative Medicine and Cellular Longevity

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Ferroptosis is a new form of regulated cell death, which is mediated by intracellular iron. Although it is reported that bavachin has antitumour effects on several tumour cells and prompts the reactive oxygen species (ROS) generation, it is unclear whether ferroptosis can be induced by bavachin in osteosarcoma (OS) cells. In this study, we found that bavachin inhibits the viability of MG63 and HOS OS cell lines along with an increase in the ferrous iron level, ROS accumulation, malondialdehyde overexpression, and glutathione depletion. Moreover, iron chelators (deferoxamine), antioxidants (Vit E), and ferroptosis inhibitors (ferrostatin-1 and liproxstatin-1) reverse bavachin-induced cell death. Bavachin also altered the mitochondrial morphology of OS cells, leading to smaller mitochondria, higher density of the mitochondrial membrane, and reduced mitochondrial cristae. Further investigation showed that bavachin upregulated the expression of transferrin receptor, divalent metal transporter-1, and P53, along with downregulating the expression of ferritin light chain, ferritin heavy chain, p-STAT3 (705), SLC7A11, and glutathione peroxidase-4 in OS cells. More importantly, STAT3 overexpression, SLC7A11 overexpression, and pretreatment with pifithrin-α (P53 inhibitor) rescued OS cell ferroptosis induced by bavachin. The results show that bavachin induces ferroptosis via the STAT3/P53/SLC7A11 axis in OS cells.

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Section: Introductionmentioning

confidence: 99%

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Luo

Gao

Zou

et al. 2021

Oxidative Medicine and Cellular Longevity

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“…In addition, a line of evidence from several researches demonstrate the ferroptotic cells could interact with immune cells, such as CD8 + T cells, by releasing chemotaxis, and then modulating the anticancer immunity [ 17 – 21 ]. Lately, ferroptosis was found to be induced in anaplastic thyroid cancer (ATC) by vitamin C via the inactivation of GPX4, reactive oxygen species (ROS) accumulation and iron sustained lipid peroxidation [ 22 ]. Numerous studies have reported that ferroptosis-related genes (FRGs) play a pivotal role in predicting tumor prognosis [ 23 – 25 ], however, the association between FRGs and prognosis in patients with PTC remains to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma

Shi

Sheng

et al. 2021

Cancer Cell Int

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Background Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer (TC), accounting for more than 80% of all cases. Ferroptosis is a novel iron-dependent and Reactive oxygen species (ROS) reliant type of cell death which is distinct from the apoptosis, necroptosis and pyroptosis. Considerable studies have demonstrated that ferroptosis is involved in the biological process of various cancers. However, the role of ferroptosis in PTC remains unclear. This study aims at exploring the expression of ferroptosis-related genes (FRG) and their prognostic values in PTC. Methods A ferroptosis-related gene signature was constructed using lasso regression analysis through the PTC datasets of the Cancer Genome Atlas (TCGA). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to investigate the bioinformatics functions of significantly different genes (SDG) of ferroptosis. Additionally, the correlations of ferroptosis and immune cells were assessed through the single-sample gene set enrichment analysis (ssGSEA) and CIBERSORT database. Finally, SDG were test in clinical PTC specimens and normal thyroid tissues. Results LASSO regression model was utilized to establish a novel FRG signature with 10 genes (ANGPTL7, CDKN2A, DPP4, DRD4, ISCU, PGD, SRXN1, TF, TFRC, TXNRD1) to predicts the prognosis of PTC, and the patients were separated into high-risk and low-risk groups by the risk score. The high-risk group had poorer survival than the low-risk group (p < 0.001). Receiver operating characteristic (ROC) curve analysis confirmed the signature's predictive capacity. Multivariate regression analysis identified the prognostic signature-based risk score was an independent prognostic indicator for PTC. The functional roles of the DEGs in the TGCA PTC cohort were explored using GO enrichment and KEGG pathway analyses. Immune related analysis demonstrated that the most types of immune cells and immunological function in the high-risk group were significant different with those in the low-risk group. Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) verified the SDG have differences in expression between tumor tissue and normal thyroid tissue. In addition, cell experiments were conducted to observe the changes in cell morphology and expression of signature’s genes with the influence of ferroptosis induced by sorafenib. Conclusions We identified differently expressed FRG that may involve in PTC. A ferroptosis-related gene signature has significant values in predicting the patients’ prognoses and targeting ferroptosis may be an alternative for PTC’s therapy.

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“…These features are both considered appealing therapeutic targets per se, and opportunities for synergistic interventions. Two emerging, related therapeutic strategies based on these phenotypic alterations of tumor cells are the use of ascorbate (for which certain tumor cells, such as glioblastomas, exhibit paradoxical differential toxicity through oxidative damage) [162,163] and other strategies leveraging on mechanisms driving ferroptosis, a specific cell-death program triggered by iron-dependent accumulation of peroxidized lipid species [164][165][166]. Autophagy can frequently act as a pro-survival response counteracting these damaging stimuli in different types of tumors [167,168].…”

Section: The Autophagolysosomal System and Cellular Ros Homeostasismentioning

confidence: 99%

“…Autophagy can frequently act as a pro-survival response counteracting these damaging stimuli in different types of tumors [167,168]. However, autophagy itself can be both positively or negatively modulated by these forms of oxidative stress, and may serve as part of the effector mechanism of the ferroptotic cascade [162,[169][170][171][172]. Further research is thus warranted to understand the architecture of the underlying networks and the principles of their functioning.…”

Section: The Autophagolysosomal System and Cellular Ros Homeostasismentioning

confidence: 99%

Autophagy and the Lysosomal System in Cancer

Kumar

Sánchez-Álvarez

Lolo

et al. 2021

Cells

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Autophagy and the lysosomal system, together referred to as the autophagolysosomal system, is a cellular quality control network which maintains cellular health and homeostasis by removing cellular waste including protein aggregates, damaged organelles, and invading pathogens. As such, the autophagolysosomal system has roles in a variety of pathophysiological disorders, including cancer, neurological disorders, immune- and inflammation-related diseases, and metabolic alterations, among others. The autophagolysosomal system is controlled by TFEB, a master transcriptional regulator driving the expression of multiple genes, including autophagoly sosomal components. Importantly, Reactive Oxygen Species (ROS) production and control are key aspects of the physiopathological roles of the autophagolysosomal system, and may hold a key for synergistic therapeutic interventions. In this study, we reviewed our current knowledge on the biology and physiopathology of the autophagolysosomal system, and its potential for therapeutic intervention in cancer.

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Vitamin C induces ferroptosis in anaplastic thyroid cancer cells by ferritinophagy activation

Cited by 54 publications

References 21 publications

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Bavachin Induces Ferroptosis through the STAT3/P53/SLC7A11 Axis in Osteosarcoma Cells

Ferroptosis-related gene signature predicts the prognosis of papillary thyroid carcinoma

Autophagy and the Lysosomal System in Cancer

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