Ferroptosis represents a non-apoptotic form of programmed cell death characterized by iron-dependent lipid peroxidation. This cell death modality not only facilitates the direct elimination of cancer cells, but also enhances their susceptibility to other pharmacological anti-cancer agents. The burgeoning interest in ferroptosis has been driven by a growing body of evidence that underscores the efficiency and minimal toxicity of ferroptosis inducers. Traditional inducers, such as erastin and RSL3 have shown substantial promise in clinical applications due to their potent therapeutic effects. Their significant potential of these inducers has spurred the development of a variety of small molecule ferroptosis inducers. These novel inducers boast an enhanced structural variety, improved metabolic stability, the capability to initiate ferroptosis without triggering apoptosis, making them well-suited for in vivo use. Despite these advancements, challenges still remain, particularly concerning the drug delivery, tumor specificity, and circulation duration of these small molecules in vivo. Addressing these challenges, contemporary research has pivoted towards innovative delivery systems tailored for ferroptosis inducers to facilitate precise, targeted, and synegestic therapeutic delivery. This review scrutinizes the latest progress in small molecule ferroptosis inducers and nano drug delivery systems geared towards ferroptosis sensitization. Furthermore, it delineated the prospective therapeutic advantages and the existing hurdles in the development of ferroptosis inducers for malignant tumor treatment.
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http://dx.doi.org/10.1016/j.bioorg.2024.107331 | DOI Listing |
Neoplasma
December 2024
Department of Gastrointestinal Surgery, Renmin Hospital of Wuhan University, Wuchang, Wuhan, Hubei, China.
Many lines of evidence suggest that circular RNAs (circRNAs) are closely associated with the occurrence and progression of colon cancer. The objective of this study was to investigate the regulatory effects and mechanisms of circ_0075829 on ferroptosis and immune escape in colon cancer. We utilized colon cancer cell lines and a xenograft mouse model to analyze the function of circ_0075829 in vitro and in vivo.
View Article and Find Full Text PDFNanoscale
January 2025
School of Chemistry and Chemical Engineering, Center of Free Electron Laser & High Magnetic Field, Key Laboratory of Structure and Functional Regulation of Hybrid Materials Ministry of Education, Key Laboratory of Functional Inorganic Materials Chemistry of Anhui Province, and Key Laboratory of Chemistry for Inorganic/Organic Hybrid Functionalized Materials of Anhui Province, Anhui University, P.R. China.
Currently, the study of cuproptosis focuses on the Cu-induced morphology changes in mitochondria (Mito), and the observation of the effect of endoplasmic reticulum (ER)-related Cu content on cuproptosis is relatively lacking. Herein, we have developed a hydroxyflavone (HF)-based NIR excited two-photon fluorescent probe, BHCO, that exhibits specific recognition of Cu with high resolution. BHCO-Cu (Cu2BC) can lead to DLAT protein aggregation, triggering cuproptosis.
View Article and Find Full Text PDFTransl Lung Cancer Res
December 2024
Department of Thoracic Surgery, Affiliated Hospital of Nantong University, Medical School of Nantong University, Nantong, China.
Background: Lung adenocarcinoma (LUAD) is the most common subtype of non-small cell lung cancer (NSCLC) and accounts for about 40% of all lung cancer cases. This research aims to investigate the effects of miR-9-3p on ferroptosis in LUAD cells and to elucidate its regulatory mechanisms. Studies have shown that LUAD is related to ferroptosis, and specific microRNAs (miRNA) are also related to ferroptosis.
View Article and Find Full Text PDFBackground: Non-small-cell lung cancer (NSCLC) remains a deadly malignancy worldwide. Resistance to cisplatin (DDP) is a significant obstacle that limits the therapeutic efficacy in NSCLC patients.
Objectives: This study investigated the role and mechanism of 24-dehydrocholesterol reductase (DHCR24) in DDP resistance in NSCLC cells.
Lipid droplets (LDs) are organelles that store and supply lipids based on cellular needs. While mechanisms preventing oxidative damage to membrane phospholipids are established, the vulnerability of LD neutral lipids to peroxidation and protective mechanisms are unknown. Here, we identify LD-localized Ferroptosis Suppressor Protein 1 (FSP1) as a critical regulator that prevents neutral lipid peroxidation by recycling coenzyme Q10 (CoQ10) to its lipophilic antioxidant form.
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