Phytomedicine, Год журнала: 2024, Номер 136, С. 156303 - 156303
Опубликована: Дек. 4, 2024
Abnormal antioxidant capacity in cancer cells is intimately linked to tumor aggressiveness. Modulating oxidative stress status and inhibiting ferroptosis represents a novel anticancer therapeutic strategy. STAM Binding Protein Like 1 (STAMBPL1), deubiquitinase, implicated various malignancies, yet its function potential for cholangiocarcinoma (CCA) remains unexplored.
Язык: Английский
Molecular Cancer, Год журнала: 2024, Номер 23(1)
Опубликована: Сен. 6, 2024
Язык: Английский
Процитировано
46
Redox Biology, Год журнала: 2024, Номер 75, С. 103259 - 103259
Опубликована: Июнь 27, 2024
Ferroptosis is a form of iron-related oxidative cell death governed by an integrated redox system, encompassing pro-oxidative proteins and antioxidative proteins. These undergo precise control through diverse post-translational modifications, including ubiquitination, phosphorylation, acetylation, O-GlcNAcylation, SUMOylation, methylation, N-myristoylation, palmitoylation, modification. modifications play pivotal roles in regulating protein stability, activity, localization, interactions, ultimately influencing both the buildup iron lipid peroxidation. In mammalian cells, regulators ferroptosis typically degradation via two principal pathways: ubiquitin-proteasome which handles majority degradation, autophagy, primarily targeting long-lived or aggregated This comprehensive review aims to summarize recent advances modification linked ferroptosis. It also discusses strategies for modulating systems, providing new insights into potential therapeutic applications cancer non-neoplastic diseases.
Язык: Английский
Процитировано
16
Antioxidants, Год журнала: 2024, Номер 13(6), С. 697 - 697
Опубликована: Июнь 6, 2024
Glutathione (GSH), a prominent antioxidant in organisms, exhibits diverse biological functions and is crucial safeguarding cells against oxidative harm upholding stable redox milieu. The metabolism of GSH implicated numerous diseases, particularly the progression malignant tumors. Consequently, therapeutic strategies targeting regulation synthesis to modulate levels represent promising avenue for future research. This study aimed elucidate intricate relationship between ferroptosis, highlighting how modulation can impact cellular susceptibility ferroptosis consequently influence development tumors other diseases. paper provides comprehensive overview physiological GSH, including its structural characteristics, physicochemical properties, sources, metabolic pathways, as well investigate molecular mechanisms underlying potential interventions. Unraveling role holds promise individuals afflicted with
Язык: Английский
Процитировано
14
Life Sciences, Год журнала: 2025, Номер unknown, С. 123565 - 123565
Опубликована: Март 1, 2025
Язык: Английский
Процитировано
1
European Journal of Pharmacology, Год журнала: 2024, Номер 972, С. 176553 - 176553
Опубликована: Апрель 2, 2024
Stroke poses a significant risk of mortality, particularly among the elderly population. The pathophysiological process ischemic stroke is complex, and it crucial to elucidate its molecular mechanisms explore potential protective drugs. Ferroptosis, newly recognized form programmed cell death distinct from necrosis, apoptosis, autophagy, closely associated with pathophysiology stroke. N6022, selective inhibitor S-nitrosoglutathione reductase (GSNOR), "first-in-class" drug for asthma therapeutic applications. However, remains unclear whether N6022 exerts effects in stroke, precise action are unknown. This study aimed investigate mitigates cerebral ischemia/reperfusion (I/R) injury by reducing ferroptosis underlying mechanisms. Accordingly, we established an oxygen-glucose deprivation/reperfusion (OGD/R) model middle artery occlusion/reperfusion (MCAO/R) mouse mimic I/R injury. Our data, both vitro vivo, demonstrated that effectively protected against I/R-induced brain damage neurological deficits mice, as well OGD/R-induced BV2 damage. Mechanistically, promoted Nrf2 nuclear translocation, enhancing intracellular antioxidant capacity SLC7A11-GPX4 system. Furthermore, interfered interaction GSNOR GSTP1, thereby boosting GSTP1 attenuating ferroptosis. These findings provide novel insights, showing attenuates microglial induced through promotion translocation inhibition GSNOR/GSTP1 axis.
Язык: Английский
Процитировано
9
International Journal of Biological Macromolecules, Год журнала: 2024, Номер 276, С. 133792 - 133792
Опубликована: Июль 9, 2024
Язык: Английский
Процитировано
8
Phytomedicine, Год журнала: 2024, Номер 134, С. 155989 - 155989
Опубликована: Авг. 31, 2024
Язык: Английский
Процитировано
8
Frontiers in Pharmacology, Год журнала: 2024, Номер 15
Опубликована: Сен. 30, 2024
Cancer, the world’s second leading cause of death after cardiovascular diseases, is characterized by hallmarks such as uncontrolled cell growth, metastasis, angiogenesis, hypoxia, and resistance to therapy. Autophagy, a cellular process that can both support inhibit cancer progression, plays critical role in development progression. This involves formation autophagosomes ultimately fuse with lysosomes degrade components. A key regulator this Sirtuin 1 (SIRT1), which significantly influences autophagy. review delves into SIRT1 modulating autophagy its broader impacts on carcinogenesis. regulates crucial mediators, AMP-activated protein kinase (AMPK) mammalian target rapamycin (mTOR), effectively promoting or suppressing Beyond direct effects autophagy, SIRT1’s regulatory actions extend other processes, including apoptosis ferroptosis, thereby influencing tumor proliferation, chemotherapy responses. These insights underscore complex interplay between significant implications for Targeting associated pathways presents promising strategy manipulate treatment. underscores potential therapeutic target, opening new avenues enhancing treatment efficacy.
Язык: Английский
Процитировано
5
Pharmacological Research, Год журнала: 2024, Номер 210, С. 107490 - 107490
Опубликована: Ноя. 5, 2024
The emergence of sorafenib resistance has become a predominant impediment and formidable dilemma in the therapeutic approach for hepatocellular carcinoma (HCC). Although approval next-generation drugs as alternatives to is significant development, concurrent use inhibitors that target additional key molecular pathways remains an effective strategy mitigate acquisition resistance. Here, we identified Glutathione S-Transferase Alpha 1 (GSTA1) critical modulator (SR) (HCC) based on our findings from experiments conducted recurrent liver cancer tissues, xenograft mouse models, organoids, sorafenib-resistant cells. Elevated GSTA1 levels are strongly associated with adverse clinical prognoses. knockout reinstates sensitivity, whereas its overexpression attenuates drug efficacy. Mechanistically, enhances accumulation lipid peroxides suppresses ferroptosis by exerting peroxidase function regulate SR. Notably, upregulation expression mediated transcription factor CTNNB1 (β-catenin), resulting formation cytoplasmic complex between CTNNB1. This facilitates nuclear translocation CTNNB1, establishing positive feedback loop. combined demonstrated synergistic anti-tumour effects through induction both vitro vivo. Our reveal novel regulatory role GSTA1/CTNNB1 axis ferroptosis, suggesting targeting could be promising circumvent HCC.
Язык: Английский
Процитировано
4
Heliyon, Год журнала: 2024, Номер 10(14), С. e34397 - e34397
Опубликована: Июль 1, 2024
Multiple myeloma (MM) is an incurable malignancy of plasma cells that sensitive to T-5224, AP-1 inhibitor. Previous study indicated T-5224 inhibits proliferation and induces apoptosis in MM cells. However, the high mortality cannot be fully explained. To date, no studies have investigated ferroptosis induced by MM. Therefore, we further mechanism which kills We observed exhibits antimyeloma properties both vitro vivo. T-5224-induced cell death was reversed ferroptosis-specific inhibitor ferropstatin-1 (Fer-1). The protein levels key regulators GPX4 SLC7A11 were decreased Furthermore, reduced phosphorylation PI3K AKT signaling pathway components, ultimately causing death. Using 740 Y–P, a activator, Fer-1, inhibitor, discovered through PI3K/AKT pathway. Bortezomib (BTZ), FDA-approved drug for treatment, can administered combination with other agents. evaluated synergistic effect BTZ combined inhibitors on Our findings provide better theoretical basis potential new perspective treatment.
Язык: Английский
Процитировано
3