Butyrate dictates ferroptosis sensitivity through FFAR2-mTOR signaling DOI Creative Commons

GuoYan Wang,

Senlin Qin,

Lei Chen

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(4)

Published: April 25, 2023

Evidence shows that short-chain fatty acids (SCFAs) play an important role in health maintenance and disease development. In particular, butyrate is known to induce apoptosis autophagy. However, it remains largely unclear whether can regulate cell ferroptosis, the mechanism by which has not been studied. this study, we found RAS-selective lethal compound 3 (RSL3)- erastin-induced ferroptosis were enhanced sodium (NaB). With regard underlying mechanism, our results showed NaB promoted inducing lipid ROS production via downregulating expression of solute carrier family 7 member 11 (SLC7A11) glutathione peroxidase 4 (GPX4). Moreover, FFAR2-AKT-NRF2 axis FFAR2-mTORC1 accounts for NaB-mediated downregulation SLC7A11 GPX4, respectively, a cAMP-PKA-dependent manner. Functionally, inhibit tumor growth inhibitory effect could be eliminated administrating MHY1485 (mTORC1 activator) Ferr-1 (ferroptosis inhibitor). Altogether, vivo suggest treatment correlated mTOR-dependent consequent through xenografts colitis-associated colorectal tumorigenesis, implicating potential clinical applications future cancer treatments. Based on all these findings, have proposed regulatory inhibits mTOR pathway control tumorigenesis.

Language: Английский

Thirty years of NRF2: advances and therapeutic challenges DOI
Donna D. Zhang

Nature Reviews Drug Discovery, Journal Year: 2025, Volume and Issue: unknown

Published: March 4, 2025

Language: Английский

Citations

6
Targeting estrogen-regulated system xc− promotes ferroptosis and endocrine sensitivity of ER+ breast cancer DOI Creative Commons
Jiawei Cao, Tong Zhou, Tom Wu

et al.

Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)

Published: Jan. 20, 2025

Abstract Estrogen receptor positive (ER+) breast cancer accounts for approximately 70% of cases. Endocrine therapies targeting estrogen are the first line ER+ cancer. However, resistance to these occurs in about half patients, leading decreased survival rates. Inducing ferroptosis is a promising therapeutic strategy treatment refractory and malignant cancers including triple-negative Nevertheless, relatively resistant inducers. Here, we uncovered that ERα suppressed Silencing triggered ferroptosis, which was attenuated by inhibitor Ferrostatin-1, enhanced inducer Erastin. Mechanistically, transcriptionally upregulated expression SLC7A11 SLC3A2, two subunits system x c − , one key inhibitory regulator ferroptosis. Overexpression exogenous SLC3A2 able mitigate induced inhibition. Moreover, levels were elevated endocrine-resistant cells tumors. Importantly, Sorafenib or Imidazole ketone erastin effectively inhibited growth tamoxifen-resistant vitro vivo. In conclusion, our data reveal estrogen-regulated enhances cancer, offering novel option patients with particularly those endocrine resistance.

Language: Английский

Citations

2
Targeting YBX1‐m5C mediates RNF115 mRNA circularisation and translation to enhance vulnerability of ferroptosis in hepatocellular carcinoma DOI Creative Commons
Ouwen Li, Ke An, Han Wang

et al.

Clinical and Translational Medicine, Journal Year: 2025, Volume and Issue: 15(3)

Published: March 1, 2025

Abstract Background RNA 5‐methylcytosine (m5C) plays an important role in the progression of hepatocellular carcinoma (HCC). Dysregulation ferroptosis is closely associated with HCC. However, effect epigenetic mRNA m5C modification on HCC remains unclear. Methods In this study, was evaluated by detecting lipid reactive oxygen species (lipid ROS), ferrous ion and 4‐hydroxynonenal (4‐HNE) xenograft mouse model, diethylnitrosamine (DEN)‐initiated model so forth. The regulatory mechanisms YBX1 translation were elucidated using sequencing, ribosome immunoprecipitation (RIP)‐sequencing, bisulphite sequencing (IP)–mass spectrometry assays. Dual‐luciferase reporter, RIP‐qPCR, Co‐IP, pulldown methylated (MeRIP)‐quantitative polymerase chain reaction (qPCR) assays performed to validate mechanism regulating modification. Results Here, we found that promoted Ring Finger Protein 115 (RNF115) through modification, thereby inhibiting promoting development. Moreover, RNF115 identified as E3 ubiquitin ligase for dihydroorotate dehydrogenase (DHODH), Lys27 (K27) ubiquitination its autophagic degradation counteract ferroptosis. addition, bound sites 3′‐untranslated region (UTR) interacted Eukaryotic Translation Initiation Factor 4A1 (EIF4A1) bridge 5′‐UTR regions, circularisation translation, while NOP2/Sun methyltransferase 2 (NSUN2) responsible Conclusions current work revealed m5C‐dependent manner, DHODH expression suppress This research sheds light m5C‐modified mRNAs ferroptosis, highlighting promise a biomarker prognosis target therapy Key points inhibits RNF115‐DHODH axis. RNF115, ligase, mediates K27 DHODH. binds 3′‐UTR interacts EIF4A1 5′‐UTR, translation. High YBX1/RNF115 predicts poor overall survival

Language: Английский

Citations

2
Molecular pathways associated with oxidative stress and their potential applications in radiotherapy (Review) DOI Creative Commons
Rui Liu,

Yan Bian,

Lin Liu

et al.

International Journal of Molecular Medicine, Journal Year: 2022, Volume and Issue: 49(5)

Published: March 15, 2022

Radiotherapy is an essential and effective treatment modality for cancer. Excessive levels of reactive oxygen species (ROS) induced by ionizing radiation disrupt the redox homeostasis lead to oxidative stress that may result in cell death. However, tumor microenvironment dynamic responds radiotherapy activating numerous cellular signaling pathways. By scavenging excess ROS, activity endogenous antioxidant enzymes radioresistance worsen clinical outcomes. To assess full potential radiotherapy, it explore underlying mechanisms target identification. The present review article summarized recent data demonstrating nuclear factor‑erythroid factor 2‑related 2 (Nrf2) as a powerful transcription one major defense protect against response radiotherapy; glutathione (GSH) thioredoxin (Trx) systems complement each other are associated with protection cancer cells from damage. In addition, suggested dual targeting inhibit GSH Trx be strategy development radiosensitive radioprotective drugs.

Language: Английский

Citations

50
Ferritinophagy is involved in Bisphenol A-induced ferroptosis of renal tubular epithelial cells through the activation of the AMPK-mTOR-ULK1 pathway DOI
Lijuan Bao, Caijun Zhao,

Lianjun Feng

et al.

Food and Chemical Toxicology, Journal Year: 2022, Volume and Issue: 163, P. 112909 - 112909

Published: March 12, 2022

Language: Английский

Citations

49
The Role of SLC7A11 in Cancer: Friend or Foe? DOI Open Access
Sijia Li, Zhenyao Lu, Runbin Sun

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(13), P. 3059 - 3059

Published: June 22, 2022

SLC7A11 controls the uptake of extracellular cystine in exchange for glutamate at a ratio 1:1, and it is overexpressed variety tumours. Accumulating evidence has shown that expression fine-tuned multiple levels, plays diverse functional pharmacological roles tumours, such as cellular redox homeostasis, cell growth death, metabolism. Many reports have suggested inhibition activity favourable tumour therapy; thus, regarded potential therapeutic target. However, emerging also suggests on some occasions, beneficial to survival cancer cells, confers development drug resistance. In this review, we first briefly introduce biological properties SLC7A11, including its structure physiological functions, further summarise regulatory network regulators. Then, focusing role cancer, describe relationships with tumourigenesis, survival, proliferation, metastasis, resistance more detail. Finally, since been linked through approaches, propose contribution mechanism require elucidation. Thus, personalised strategies should be adapted when targeting SLC7A11.

Language: Английский

Citations

47
Targeting stearoyl-coa desaturase enhances radiation induced ferroptosis and immunogenic cell death in esophageal squamous cell carcinoma DOI Creative Commons
Hui Luo, Xiaohui Wang, Shuai Song

et al.

OncoImmunology, Journal Year: 2022, Volume and Issue: 11(1)

Published: July 15, 2022

Overcoming resistance to radiation is a major challenge in cancer treatment. Stearoyl-coa desaturase (SCD1) the enzyme responsible for oleic acid (OA) and palmitoleic (POA) formation. Here, we provided evidence that targeting SCD1 was capable of inducing ferroptosis immunogenic cell death (ICD), thereby improving sensitivity esophageal squamous carcinoma (ESCC). ESCC lines with high expression were treated MF-438 (SCD1 inhibitor) determine viability. Colony formation assay performed evaluate sensitization inhibitor. Tumor ICD analyzed MF-438, therapy (RT) combination treatment group. The potential molecular mechanisms underlying as novel sensitizer explored. We concluded by assessing prognostic factor ESCC. exhibited antitumor activity cells. Our outcomes revealed significant improvement MF-438. Moreover, enhanced tumor ICD. Further analyses conferred via alleviating cells; inhibited biosynthesis OA POA, improved induced Clinical analysis indicated associated unfavorable survival patients In summary, our results demonstrated acted inducer. Targeting immunogenicity ferroptotic cells increased effectiveness RT could be considered useful indicator

Language: Английский

Citations

43
Radiotherapy modulates tumor cell fate decisions: a review DOI Creative Commons
Hao Chen, Zhongyu Han, Qian Luo

et al.

Radiation Oncology, Journal Year: 2022, Volume and Issue: 17(1)

Published: Dec. 1, 2022

Abstract Cancer has always been a worldwide problem, and the application of radiotherapy greatly improved survival rate cancer patients. Radiotherapy can modulate multiple cell fate decisions to kill tumor cells achieve its therapeutic effect. With development technology, how increase killing effect reduce side effects on normal become new problem. In this review, we summarize mechanisms by which induces apoptosis, necrosis, necroptosis, pyroptosis, ferroptosis, autophagy, senescence, mitotic catastrophe, cuproptosis. An in-depth understanding these radiotherapy-related improve efficiency for cancer.

Language: Английский

Citations

42
Nrf2 signaling pathway: current status and potential therapeutic targetable role in human cancers DOI Creative Commons
Lin Li, Qing Wu,

Feifei Lu

et al.

Frontiers in Oncology, Journal Year: 2023, Volume and Issue: 13

Published: Sept. 22, 2023

Cancer is a borderless global health challenge that continues to threaten human health. Studies have found oxidative stress (OS) often associated with the etiology of many diseases, especially aging process and cancer. Involved in OS reaction as key transcription factor, Nrf2 pivotal regulator cellular redox state detoxification. can prevent damage by regulating gene expression antioxidant response elements (ARE) promote process. generated an imbalance promotes accumulation mutations genome instability, thus establishment development different cancers. activation regulates plethora processes inducing proliferation, differentiation death, strongly OS-mediated What’s more, also involved anti-inflammatory effects metabolic disorders, neurodegenerative multidrug resistance. highly expressed multiple body parts digestive system, respiratory reproductive system nervous system. In oncology research, has emerged promising therapeutic target. Therefore, certain natural compounds drugs exert anti-cancer through signaling pathway, blocking pathway reduce some types tumor recurrence rates increase sensitivity chemotherapy. However, Nrf2’s dual role controversial impact cancer are inevitable consideration factors when treating this review, we summarized current biological characteristics its mechanism cells, discussed Keap1/Nrf2/ARE downstream genes, elaborated related pathways such AMPK/mTOR NF-κB. Besides, main target strategies using inhibitors or activators, well possible positive negative were reviewed. It be concluded serves important factor formation development, provides basis for targeted therapy

Language: Английский

Citations

42
The amino acid transporter SLC7A11-mediated crosstalk implicated in cancer therapy and the tumor microenvironment DOI

Jiaqin He,

Xiaomeng Wang, Keying Chen

et al.

Biochemical Pharmacology, Journal Year: 2022, Volume and Issue: 205, P. 115241 - 115241

Published: Sept. 6, 2022

Language: Английский

Citations

41