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CHAC1: a master regulator of oxidative stress and ferroptosis in human diseases and cancers.

CHAC1, an essential regulator of oxidative stress and ferroptosis, is increasingly recognized for its significant roles in these cellular processes and its impact on various human diseases and cancers. This review aims to provide a comprehensive overview of CHAC1's molecular functions, regulatory mechanisms, and effects in different pathological contexts. Specifically, the study objectives are to elucidate the biochemical pathways involving CHAC1, explore its regulatory network, and discuss its implications in disease progression and potential therapeutic strategies. As a γ-glutamyl cyclotrans

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… CHAC1-mediated macrophage apoptosis is critical for reducing inflammation and preventing fibrosis in the R213G variant model | Allawzi et al. (2019) Bronchopulmonary Dysplasia (BPD) | A549 (human alveolar epithelial cells) | In vivo (C57BL/6J neonatal mice), In vitro (A549 cells) | Suppresses ferroptosis …

Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

Genus Sophora: a comprehensive review on secondary chemical metabolites and their biological aspects from past achievements to future perspectives.

Sophora is deemed as one of the most remarkable genera of Fabaceae, and the third largest family of flowering plants. The genus Sophora comprises approximately 52 species, 19 varieties, and 7 forms that are widely distributed in Asia and mildly in Africa. Sophora species are recognized to be substantial sources of broad spectrum biopertinent secondary metabolites namely flavonoids, isoflavonoids, chalcones, chromones, pterocarpans, coumarins, benzofuran derivatives, sterols, saponins (mainly triterpene glycosides), oligostilbenes, and mainly alkaloids. Meanwhile, extracts and isolated compoun

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers.

Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer's disease or myasthenia gravis will be discuss

Bioinformatics-Guided Discovery of miRNAs Involved in Apoptosis Modulated by Parthenolide Combined with Vincristine in The NALM6 Cell Line.

ObjectiveAcute lymphoblastic leukemia (ALL) is a highly heterogeneous leukemia. Despite the current improvement in conventional chemotherapy and high survival rates, the outcomes remain challenging. Sesquiterpen extracted from the Tanacetum parthenium, parthenolide, is a potential anticancer agent that can modulate the expression of miRNAs and induce apoptosis. The objective of this study was to investigate the effect of parthenolide in combination with vincristine and alone on the apoptosis rate and expression of miR-125b-5p, miR-181b-5p, and miR-17-5p in the NALM6 cell line.Materials and met

Integrating Narcissus-derived galanthamine production into traditional upland farming systems.

Alzheimer's disease (AD) is a disorder associated with progressive degeneration of memory and cognitive function. Galantamine is a licenced treatment for AD but supplies of the plant alkaloid that it is produced from, galanthamine, are limited. This three-year system study tested the potential to combine Narcissus-derived galanthamine production with grassland-based ruminant production. Replicate plots of permanent pasture were prepared with and without bulbs of Narcissus pseudonarcissus sown as lines into the sward. Two different fertiliser regimes were imposed. The above-ground green biomass

What nature has to offer: Opportunities for immuno-oncology.

Recent rapid development of cancer therapy has come about with the paradigm shift from the traditional goal of targeting cancer cells themselves, to reprograming the immune tumor microenvironment. Accumulating evidence shows that compounds that target epigenetic regulation, called epidrugs, play a crucial role in mediating the immunogenicity of cancer cells and in reshaping antitumor immunity. A large body of literature has recognized natural compounds as epigenetic modulators for their immunomodulatory effects and anticancer potential. Unifying our understanding of the role of these biologica

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… Sodium butyrate combined with docetaxel for the treatment of lung adenocarcinoma A549 cells by targeting Gli1. OncoTargets Ther. 2020;13:8861. doi: 10.2147/OTT.S252323. 113. Amin A, Wang D, Nannapaneni S, Lamichhane R, Chen ZG, Shin DM. …

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran.

Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3'-Geranyl-3-prenyl-5,7,2',4'-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate

Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy.

Despite the great advancements made in cancer treatment, there are still many unsatisfied aspects, such as the wide palette of side effects and the drug resistance. There is an obvious increasing scientific attention towards nature and what it can offer the human race. Natural products can be used to treat many diseases, of which some plant products are currently used to treat cancer. Plants produce secondary metabolites for their signaling mechanisms and natural defense. A variety of plant-derived products have shown promising anticancer properties in vitro and in vivo. Rather than recreating

Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target.

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underl

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… Expression of SDH decreases in A549 cells transfected with miR-210, resulting in a lower activity of Complex II [ 113 ]. In addition to Complex I and II, Complex IV subunits, COX10 and NDUFA4, have been identified as miR-210 targets [ 114 , 115 ]. …

Multifunctionality of Calebin A in inflammation, chronic diseases and cancer.

Chronic diseases including cancer have high case numbers as well as mortality rates. The efficient treatment of chronic diseases is a major ongoing medical challenge worldwide, because of their complexity and many inflammatory pathways such as JNK, p38/MAPK, MEK/ERK, JAK/STAT3, PI3K and NF-κB among others being implicated in their pathogenesis. Together with the versatility of chronic disease classical mono-target therapies are often insufficient. Therefore, the anti-inflammatory as well as anti-cancer capacities of polyphenols are currently investigated to complement and improve the effect of

Interpreting clinical assays for histone deacetylase inhibitors.

As opposed to genetics, dealing with gene expressions by direct DNA sequence modifications, the term epigenetics applies to all the external influences that target the chromatin structure of cells with impact on gene expression unrelated to the sequence coding of DNA itself. In normal cells, epigenetics modulates gene expression through all development steps. When "imprinted" early by the environment, epigenetic changes influence the organism at an early stage and can be transmitted to the progeny. Together with DNA sequence alterations, DNA aberrant cytosine methylation and microRNA deregulat

Целенаправленная деградация белка разрушает ненаркомные цели, чтобы обратить вспять иммунное уклонение и терапию устойчивости к раку.

Таргетированная деградация белков (ТД) использует эндогенные протеолитические системы — систему убиквина и протеасомы и лизосомальные пути — для селективного удаления белков, вызывающих болезни, которые не реагируют на традиционное ингибирование. В онкологической иммунотерапии ТД разрушает критические иммунодепрессивные узлы в экзоцитоплазматическом, мембранном и цитоплазматическом компартментах, перепрограммируя микросреду опухоли от иммунологически «холодной» к «горячей» состоянию. Эта статья рассматривает молекулярные принципы инженерии бифункциональных деградаторов и обобщает клинические д

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… Treatment with 100 nM FRTAC for 24 hours resulted in significant degradation of CD47 protein in MDA-MB-231 and A549 cells ( 21 ) ( Figure 4 ). … The MIF-targeting PROTAC degrader MD13, leveraging the cereblon (CRBN) E3 ligase and the proteasome pathway, achieves efficient MIF degradation in non-small cell lung cancer (NSCLC) A549 cells (DC 50 ≈ 100 nM). …

Reprogramming of nitrogen metabolism in tumors: mechanisms and therapeutic implications.

Nitrogen metabolism plays a key role in maintaining normal physiological functions of the organism and cell proliferation and differentiation. Nitrogen metabolism in normal human body maintains a dynamic balance to meet the body's demand for synthesis of biological macromolecules such as proteins and nucleic acids. However, in the process of tumor development, the nitrogen metabolism of tumor cells is reprogrammed to meet the demand of rapid proliferation, showing significantly different metabolic characteristics from normal cells. Key enzymes in the tumor microenvironment affect nitrogen meta

A Narrative Review on the Antitumoral Effects of Selected Mediterranean Plant Products from Southern Italy.

Natural products are a valuable source of bioactive compounds with established roles in oncology. Their structural diversity and ability to target multiple cancer-related pathways make them promising candidates for anticancer drug development. Increasing preclinical and clinical data highlight their potential not only to exert direct antitumor effects but also to enhance patient tolerance to conventional therapies by reducing side effects and improving treatment adherence. The Mediterranean region, known for its biodiversity and traditional dietary habits, provides a rich array of natural comp

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Inhibition of Plk1 and Cyclin B1 expression results in panobinostat-induced G₂ delay and mitotic defects.

The development of clinically useful histone deacetylase inhibitors has expanded greatly. In a preclinical study, we showed that panobinostat (LBH589) inhibits cell cycle progression of human head and neck squamous cell carcinoma (HNSCC) cell lines at G₂/M and an associated decrease in expression of particular genes required for passage through G₂ and mitosis. In this study we sought to analyse the mechanistic underpinnings of panobinostat-induced growth arrest. HNSCC cell lines were synchronised and progression through mitosis monitored. We demonstrate that panobinostat causes a marked G₂ del

Influence of Hypoxia on Tumor Heterogeneity, DNA Repair, and Cancer Therapy: From Molecular Insights to Therapeutic Strategies.

Hypoxia, characterized by a reduction in tissue oxygen levels, is a hallmark of many solid tumors and affects a range of cellular processes, including DNA repair. In low-oxygen conditions, cancer cells often suppress key DNA repair pathways such as homologous recombination (HR), leading to the accumulation of DNA damage and increased genomic instability. These changes not only drive tumor progression but also contribute to resistance against conventional therapies. Hypoxia significantly reduces the effectiveness of oxygen-dependent treatments, including radiotherapy and many chemotherapeutic a

Ferroptosis in Haematological Malignancies and Associated Therapeutic Nanotechnologies.

Haematological malignancies are heterogeneous groups of cancers of the bone marrow, blood or lymph nodes, and while therapeutic advances have greatly improved the lifespan and quality of life of those afflicted, many of these cancers remain incurable. The iron-dependent, lipid oxidation-mediated form of cell death, ferroptosis, has emerged as a promising pathway to induce cancer cell death, particularly in those malignancies that are resistant to traditional apoptosis-inducing therapies. Although promising findings have been published in several solid and haematological malignancies, the major

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… Delivery of apigenin-loaded magnetic Fe2O3/Fe3O4@mSiO2 nanocomposites to A549 cells and their antitumor mechanism Mater. Sci. Eng. C 2021 120 111719 10.1016/j.msec.2020.111719 33545870 134. Zhang J. Yang J. Zuo T. Ma S. Xokrat N. Hu Z. Wang Z. Xu R. Wei Y. Shen Q. …

Repurposing of nervous system drugs for cancer treatment: recent advances, challenges, and future perspectives.

The nervous system plays a critical role in developmental biology and oncology, influencing processes from ontogeny to the complex dynamics of cancer progression. Interactions between the nervous system and cancer significantly affect oncogenesis, tumor growth, invasion, metastasis, treatment resistance, inflammation that promotes tumors, and the immune response. A comprehensive understanding of the signal transduction pathways involved in cancer biology is essential for devising effective anti-cancer strategies and overcoming resistance to existing therapies. Recent advances in cancer neurosc