Drug-induced oxidative stress in cancer treatments: Angel or devil?

Redox Biology, Journal Year: 2023, Volume and Issue: 63, P. 102754 - 102754

Published: May 18, 2023

Oxidative stress (OS), defined as redox imbalance in favor of oxidant burden, is one the most significant biological events cancer progression. Cancer cells generally represent a higher level, which suggests dual therapeutic strategy by regulating status (i.e., pro-oxidant therapy and/or antioxidant therapy). Indeed, exhibits great anti-cancer capability, attributing to accumulation within cells, whereas restore homeostasis has been claimed fail several clinical practices. Targeting vulnerability pro-oxidants capable generating excessive reactive oxygen species (ROS) surfaced an important strategy. However, multiple adverse effects caused indiscriminate attacks uncontrolled drug-induced OS on normal tissues and drug-tolerant capacity some certain greatly limit their further applications. Herein, we review representative oxidative drugs summarize side organs, emphasizing that seeking balance between damage value exploiting next-generation OS-based chemotherapeutics.

Language: Английский

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PANoptosis: Mechanisms, biology, and role in disease

Immunological Reviews, Journal Year: 2023, Volume and Issue: 321(1), P. 246 - 262

Published: Oct. 12, 2023

Summary Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which mediated by multifaceted PANoptosome complexes assembled via integrating components from other modalities. There growing interest in process function of PANoptosis. Accumulating evidence suggests that occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, cancer. Given impact across disease spectrum, this review briefly describes relationships highlights key molecules formation activation, outlines roles diseases together with potential therapeutic targeting. We also discuss important concepts pressing issues future research. Improved understanding its mechanisms crucial identifying novel targets strategies.

Language: Английский

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Inhibition of METTL3 ameliorates doxorubicin-induced cardiotoxicity through suppression of TFRC-mediated ferroptosis

Redox Biology, Journal Year: 2024, Volume and Issue: 72, P. 103157 - 103157

Published: April 12, 2024

Doxorubicin (DOX) is a chemotherapeutic drug, while its clinical use greatly limited by the life-threatening cardiotoxicity. N6-methyladenosine (m6A) RNA modification participates in varieties of cellular processes. Nonetheless, it remains elusive whether m6A and methyltransferase METTL3 are involved progression DOX-induced cardiotoxicity (DIC). Mice were administrated with DOX (accumulative dosage 20 mg/kg) repeatedly to establish chronic DIC model. Cardiomyocyte-specific conditional knockout mice employed evaluate effects altered on DIC. The cardiomyocyte ferroptosis also examined response stimulation. led increased levels expression cardiomyocytes c-Jun-dependent manner. METTL3-knockout exhibited improved cardiac function, remodeling injury following insult. Besides, inhibition alleviated iron accumulation cardiomyocytes, whereas overexpression exerted opposite effects. Mechanistically, promoted TFRC mRNA, critical gene governing uptake, enhanced stability through recognition reader protein, IGF2BP2. Moreover, pharmacological administration highly selective inhibitor STM2457 effectively ameliorated mice. plays cardinal role etiology regulating metabolism modification. Inhibition might be potential therapeutic avenue for

Language: Английский

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Metformin Alleviates Doxorubicin-Induced Cardiotoxicity via Preserving Mitochondrial Dynamics Balance and Calcium Homeostasis

Applied Biochemistry and Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 10, 2025

Abstract Doxorubicin (DOX) is a commonly used chemotherapeutic medication for treating malignancies, although its cardiotoxicity limits use. There growing evidence that alteration of the mitochondrial fission/fusion dynamic processes accompanied by excessive reactive oxygen species (ROS) production and calcium Ca 2+ homeostasis are potential underlying mechanisms DOX-induced (DIC). Metformin (Met) an AMP-activated protein kinase (AMPK) activator has antioxidant properties cardioprotective effects. The purpose study to assess Met's possible benefits against cardiotoxicity. included 32 adult male rats. They were randomly divided into four groups: administered saline, DOX, Met, or DOX combined with Met respectively. Heart tissues biochemical assays measured oxidative stress markers, malondialdehyde (MDA), reduced glutathione (GSH), dynamics optic atrophy-1(OPA-1) dynamin-1-like (Drp1), calcineurin caspase-3. Serum levels myocardial injury cardiac troponin I (cTn-I), aspartate aminotransferase (AST), also measured. results revealed intoxication was associated significant increase in serum cTn-I AST, increased MDA level, Drp1, calcineurin, caspase-3 expressions, as well GSH level OPA-1 expression. On other hand, treatment significantly DIC decreasing stress, apoptosis, improving balance. Finally, this shows may be able protect heart from damage caused working anti-apoptotic agent keeping balance mitochondria.

Language: Английский

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Rnd3 protects against doxorubicin-induced cardiotoxicity through inhibition of PANoptosis in a Rock1/Drp1/mitochondrial fission-dependent manner

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

Published: Jan. 4, 2025

Abstract Doxorubicin, a representative drug of the anthracycline class, is widely used in cancer treatment. However, Doxorubicin-induced cardiotoxicity (DIC) presents significant challenge its clinical application. Mitochondrial dysfunction plays central role DIC, primarily through disrupting mitochondrial dynamics. This study aimed to investigate impact Rnd3 (a Rho family GTPase 3) on with focus Cardiomyocyte-specific transgenic mice (Rnd3-Tg) and LSP/LSP (N-Tg) were established for vivo experiments, adenoviruses harboring (Ad-Rnd3) or negative control (Ad-Control) injected myocardium vitro experiments. The DIC model was using wild-type, N-Tg, Rnd3-Tg mice, subsequent intraperitoneal injection Dox 4 weeks. molecular mechanism explored RNA sequencing, immunofluorescence staining, co-immunoprecipitation assay, protein-protein docking. administration induced injury cardiac dysfunction, which ameliorated by overexpression. Further, augmentation expression mitigated fragmentation mediated dynamin-related protein 1 (Drp1), thereby ameliorating PANoptosis (pyroptosis, apoptosis, necroptosis) response Dox. Mechanically, interaction between Rho-associated kinase (Rock1) may impede Rock1-induced Drp1 phosphorylation at Ser616, thus inhibiting fission dysfunction. Interestingly, Rock1 knockdown nullified effects cardiomyocytes PANoptosis, as well Dox-induced remodeling elicited Rnd3. enhances resilience against stabilizing dynamics reducing PANoptosis. Our findings suggest that Rnd3/Rock1/Drp1 signaling pathway represents novel target mitigating modulating could be strategic approach safeguarding function patients undergoing

Language: Английский

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Empagliflozin attenuates trastuzumab-induced cardiotoxicity through suppression of DNA damage and ferroptosis

Life Sciences, Journal Year: 2022, Volume and Issue: 312, P. 121207 - 121207

Published: Nov. 17, 2022

Language: Английский

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Molecular Mechanisms and Therapeutic Targeting of Ferroptosis in Doxorubicin-Induced Cardiotoxicity

JACC Basic to Translational Science, Journal Year: 2024, Volume and Issue: 9(6), P. 811 - 826

Published: Jan. 3, 2024

Ferroptosis, an iron-dependent form of regulated cell death, has received increasing attention for its pathophysiologic contribution to the onset and development doxorubicin-induced cardiotoxicity. Moreover, modulation ferroptosis with specific inhibitors may provide new therapeutic opportunities Here, we will review molecular mechanisms promise targeting in

Language: Английский

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DOXORUBICIN-RELATED CARDIOTOXICITY: REVIEW OF FUNDAMENTAL PATHWAYS OF CARDIOVASCULAR SYSTEM INJURY

Cardiovascular Pathology, Journal Year: 2024, Volume and Issue: 73, P. 107683 - 107683

Published: Aug. 6, 2024

Language: Английский

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FUNDC1 alleviates doxorubicin-induced cardiotoxicity by restoring mitochondrial-endoplasmic reticulum contacts and blocked autophagic flux

Theranostics, Journal Year: 2024, Volume and Issue: 14(9), P. 3719 - 3738

Published: Jan. 1, 2024

Autophagy dysregulation is known to be a mechanism of doxorubicin (DOX)-induced cardiotoxicity (DIC). Mitochondrial-Endoplasmic Reticulum Contacts (MERCs) are where autophagy initiates and autophagosomes form. However, the role MERCs in DIC remains elusive. FUNDC1 tethering protein MERCs. We aim investigate effect DOX on cardiomyocytes explore whether it involved dysregulated DIC.

Language: Английский

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Overview of Panax ginseng and its active ingredients protective mechanism on cardiovascular diseases

Journal of Ethnopharmacology, Journal Year: 2024, Volume and Issue: 334, P. 118506 - 118506

Published: July 2, 2024

Language: Английский

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