Search Results (5,044)

The fascinating features of nanomaterials have attracted immense interest across various fields, including nanoelectronics, magnetite-aided nanocatalysis, and nanomedicine. Herein, a 10% SiO₂/g-C₃N₄/Bi₂SiO₅@Bi₂O₃ triple nanohybrid was formulated via a simple protocol employing acacia powder as a capping/fuel agent. The XRD confirmed the presence of g-C₃N₄, Bi₂SiO₅, Bi₂O₃, and SiO₅ phases, and the TEM image shows densely packed, almost spherical nanoparticles of an average size of 9.2 nm. There was activity of the SiO₂/g-C₃N₄/Bi₂SiO₅@Bi₂O₃ in the field of hydrogen generation via NaBH₄ hydrolysis, and antitumor antiproliferation activity against HepG-2 and MCF-7 cells. The graphitized Bi₂O₃/SiO₂ exhibited HGRs of 303, 615, 785, and 1740 mL min⁻¹ g⁻¹ at 20, 30, 40, and 50 °C, respectively. Hydrolyzing NaBH₄ doses of 0.3, 0.5, 0.7, and 1.0 at 40 °C resulted in a dramatic evolution at HGRs of 526, 785, 1786, and 4000 mL min⁻¹ g⁻¹, respectively. Furthermore, the g-C₃N₄/Bi₂O₃/SiO₂ antiproliferative effect against HepG-2 and MCF-7 cells showed a positive impact at 3.9 and 7.9 µg/mL, with IC₅₀ values of 82.4 and 59.6 µg/mL, respectively. Moreover, the maximum dose of 500 μg/mL of SiO₂/g-C₃N₄/Bi₂SiO₅@Bi₂O₃ resulted in 93.8% inhibition of MCF-7 cells, whereas the same dose yielded 91.7% inhibition of HepG-2 cells. It is significant to note that, given the lower cost of SiO₂/g-C₃N₄/Bi₂SiO₅@Bi₂O₃ relative to currently prescribed antitumor medications, these outcomes can be considered ideal for practical use as antitumor agents. Full article

Purpose: This study sought to extract and characterize fucoidan from brown seaweed Padina tetrastromatica for the synthesis of fucoidan–gold nanoparticles (F-AuNPs) and to assess their physicochemical properties, as well as their antioxidant, anti-inflammatory, and anticancer activities, alongside potential molecular interactions with specific cancer-related targets. Methods: The extracted fucoidan-rich fraction was characterized for its sulfate content. Citrate-stabilized plain gold nanoparticles (plain AuNPs) were prepared and characterized as non-fucoidan nanoparticle controls. Comprehensive physicochemical characterization, including UV–Vis spectroscopy, Fourier-transform infrared spectroscopy (FTIR), transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic light scattering (DLS), zeta-potential analysis, and thermogravimetric analysis (TGA), was performed on the resultant fucoidan-functionalized AuNPs (F-AuNPs). Biological activities were assessed using different techniques: antioxidant potential (Ferric Reducing Antioxidant Power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays), anti-inflammatory effects (NO inhibition in macrophages), and anticancer efficacy against HepG2 cells (MTT and flow cytometry). Potential molecular targets relevant to these activities were further explored in silico using molecular docking against key cancer-related proteins, providing hypotheses for future experimental validation. Results: The fucoidan-rich fraction showed a sulfate content of 10.08%. Strong antioxidant activity was observed, especially in FRAP (11.20 ± 0.29 mg TE g⁻¹ DW). F-AuNPs exhibited enhanced cytotoxicity against HepG2 cells (IC₅₀ 138.1 µg mL⁻¹) compared to plain AuNPs (IC₅₀ 271.2 µg mL⁻¹) and the fucoidan-rich fraction (IC₅₀ 390.2 µg mL⁻¹), inducing G1 phase arrest. In addition, F-AuNPs reduced nitric oxide production in LPS-stimulated RAW 264.7 macrophages, reaching 21.42 ± 1.29% inhibition at 100 µg mL⁻¹. As an exploratory, hypothesis-generating step, an in silico target-prioritization screen identified HPSE and MMP-2 as the highest-scoring candidate proteins, proposed solely as targets for future experimental validation. Conclusions: F-AuNPs represent a promising multifunctional nanoplatform with antioxidant, anti-inflammatory, and antiproliferative activities. The integration of in vitro biological evaluation with in silico target prediction supports the potential biomedical relevance of F-AuNPs and generates testable hypotheses regarding their molecular targets, which require experimental validation. Full article

The aim of this review is to provide a narrative analysis of the role of Lactobacillus acidophilus as an active modulating factor in the prevention and treatment of cancer and allergic diseases. The paper discusses the molecular, metabolic, and bionanotechnological mechanisms of Lactobacillus acidophilus’s anticancer and immunomodulatory effects, which define this probiotic as an essential component of modern natural and functional medicine. A narrative review of the scientific literature was conducted, mainly from 2019–2026, focusing on the results of in vitro studies and studies on preclinical in vivo models, which analyzed the effect of live L. acidophilus strains, tyndallized bacteria (paraprobiotics) and cell-free supernatant from L. acidophilus cultures on, among others, immune system signaling pathways, tissue cytokine profile, and the integrity of the gastrointestinal epithelial cell barrier (enterocytes). Results indicate that L. acidophilus exerts significant antiallergic, antiproliferative, and proapoptotic effects against many types of cancer. Among other aspects, the ability of L. acidophilus to stimulate the production of anticancer exopolysaccharides and short-chain fatty acids, which directly influence the functioning of immune cells, is covered. The article thoroughly explains the immunomodulatory effects of L. acidophilus and the ability of this probiotic to regulate cytokine profiles, which helps promote an anti-inflammatory environment crucial for maintaining intestinal homeostasis. The article also discusses the direct interaction of L. acidophilus with immune cells, such as dendritic cells and macrophages, which leads to their activation and subsequent influence on the differentiation of T lymphocytes, which play a key role in the regulation of immune processes and in the development of immune tolerance. L. acidophilus is a universal mediator of immunological and metabolic homeostasis. Its ability to synergize with conventional therapies (chemotherapy, oncolytic virotherapy) and its innovative applications in the creation of postbiotics and paraprobiotics may provide a new approach to the treatment of inflammatory, allergic, and neoplastic diseases. Further clinical studies are necessary to assess the efficacy, safety, and optimal dose of this probiotic, which are essential for the widespread use of L. acidophilus in human therapy. Full article

Dietary factors, including the consumption of isoflavones-rich foods of plant origin, may contribute to the reduced incidence of prostate cancer. Isoflavones, natural phytoestrogens often found in legumes, can modulate estrogen and androgen receptor signaling. This study aimed to evaluate the biological potential of isoflavone-rich extracts obtained from twelve species from the Fabaceae family, targeting prostate cancer cell viability, proliferation, inflammatory markers, prostate-specific antigen secretion, and 5α-reductase activity. The tested extracts showed moderate cytotoxic activity against prostate cancer cell lines, apart from highly susceptible PC3 cells, and only weak toxicity to normal prostate epithelial cells. Significant antiproliferative activity was observed, especially for Cytisus scoparius, Ononis arvensis, and Genista tinctoria, while most extracts reduced prostate-specific antigen (PSA) secretion in normal prostate cells. Furthermore, the extracts showed anti-inflammatory properties by reducing the pro-inflammatory cytokine interleukin 6 (IL-6) and improving cytokine balance indices. Multivariate analyses revealed correlations between total isoflavone content and antiproliferative activity. Full article

Background/Objectives: Cancer, a multifactorial disease with uncontrolled cell growth, oxidative stress, inflammation, genomic instability, and molecular signaling pathways, is a global health concern, leading to the ~20 million newly diagnosed cases annually. Although conventional therapy has been shown to enhance the survival rates of cancer patients, its clinical efficacy is limited by certain side effects that occur as a result of treatment, thus necessitating the exploration of plant-derived bioactive compounds for their potential as safer and alternative supportive therapeutic agents. Aloe vera, known as the plant of immortality, comprises phytochemicals, such as anthraquinones (aloe-emodin, emodin, and aloin), polysaccharides (acemannan), flavonoids, and phenolic acids, which contribute to the pharmacological effect of the compound. Methods: This review summarizes the anticancer potential of Aloe vera, and the data were retrieved from databases, such as PubMed, Google Scholar, ScienceDirect, Web of Science, and Wiley Online Library, during the time period of 2015 to 2025. Results: The literature revealed that Aloe vera and its bioactive compounds have dose-dependent cytotoxic and anti-proliferative properties against hepatocellular, cervical, colorectal, lung, breast, prostate, and hematological cancers, which are significantly mediated by apoptosis and pyroptosis induction, reactive oxygen species (ROS) production, mitochondrial dysfunction, inhibition of angiogenesis and metastasis, and the modulation of key signaling pathways, particularly PI3K/Akt, MAPK, NF-кB, p53, and Wnt/β-catenin. Furthermore, anthraquinones, including Aloe-emodin, demonstrate potent anticancer effects at micro-molar doses, and polysaccharides increase immune reactions and provide tumor immunity. Conclusions: Conclusively, Aloe vera is a promising multi-target natural compound, particularly efficient in the treatment of cancer. However, despite significant therapeutic potential, more research on pharmacokinetics, standard dose, and controlled clinical trials of Aloe vera is required to validate clinical applicability. Full article

Young barley, derived from the early vegetative stage of Hordeum vulgare L., constitutes a plant-based functional ingredient whose phytochemical profile differs markedly from that of mature grain. Two principal commercial forms exist—dried grass powder and juice-derived products—differing in matrix composition and bioactive compound concentration. This narrative review critically evaluates the current knowledge on the phytochemical composition, biological activity, and translational relevance of young barley preparations considered as a functional plant food. The phytochemical spectrum is dominated by C-glycosyl flavones, particularly saponarin and lutonarin, alongside phenolic acids, chlorophylls, enzymatic antioxidants, vitamins, and minerals. Experimental evidence implicates the modulation of redox homeostasis, inflammatory signaling, and metabolic regulators as the primary biological mechanisms. In vitro studies additionally demonstrate antiproliferative activity in human cancer cell lines and immunomodulatory properties mediated by polysaccharide-rich fractions, extending the biological profile of young barley beyond classical antioxidant activity. Although preclinical models consistently demonstrate antioxidant and metabolic effects, high experimental doses and limited preparation standardization restrict the direct extrapolation to human supplementation contexts. Available clinical trials suggest modest improvements in selected lipid, glycemic, and oxidative stress markers; yet, most are small in scale and brief in duration. Agronomic variables including fertilization strategy and soil composition represent additional, underappreciated sources of phytochemical variability and safety concern. Overall, the current evidence supports the biological plausibility of young barley as a functional plant food; yet, the clinical data remain preliminary. Future research should prioritize preparation standardization, dose–response characterization, and agronomic transparency to strengthen translational reliability. In conclusion, young barley preparations represent a biologically plausible functional plant food ingredient with preliminary clinical support, pending confirmation from adequately powered, standardised randomised controlled trials. Full article

Non-thermal millimeter-wave (MMW) irradiation represents a promising non-invasive strategy for cancer therapy, yet its effects in physiologically relevant 3D systems remain poorly defined. Here, we evaluated the biological impact of MMW exposure in 3D non-small-cell lung cancer (NSCLC) spheroids (NCI-H1299, A549) and normal WI-38 fibroblasts under active cooling to suppress bulk heating. We demonstrate that cellular responses are governed primarily by power density (PD), irradiation geometry, and genotype-dependent susceptibility. High-PD pyramidal horn (PH) irradiation (~4.9 mW/cm²) induced rapid apoptosis, metabolic collapse, and near-complete loss of clonogenic survival, whereas lower-PD waveguide (WG) irradiation (~0.6 mW/cm²) produced depth-limited, cumulative cytotoxicity. Surviving cancer cells exhibited robust senescence-associated growth arrest, particularly in p53-deficient NCI-H1299 cells, indicating a dual apoptotic–senescent anti-proliferative response. In contrast, WI-38 fibroblasts showed minimal apoptosis and only transient stress-associated senescence, confirming selective tumor vulnerability. Mechanistic modeling suggests that MMW energy couples to glycan-rich membrane domains, generating localized electromagnetic hotspots that trigger calcium influx, mitochondrial dysfunction, and depth-dependent apoptosis. These findings establish a mechanistic basis for selective, non-thermal MMW-induced cytotoxicity in 3D NSCLC models and support further preclinical development of MMW-based therapeutic strategies. Full article

Background/Objectives: mRNA display technology has emerged as a powerful platform for discovering macrocyclic peptides against intractable proteins. However, direct screening against the “undruggable” transcription factor MYC using this approach remains largely unexplored. In this study, we aimed to integrate tyrosinase-mediated cyclization with mRNA display to identify novel macrocyclic peptide inhibitors targeting MYC. Methods: We performed mRNA display combined with tyrosinase-mediated cyclization to generate macrocyclic peptides targeting MYC. Antiproliferative activity was assessed in MYC-dependent tumor cells using CCK8 assay. C-terminal fusions with a TAT-derived cell-penetrating peptide were generated to enhance cell membrane permeability. Binding affinities were measured by bio-layer interferometry (BLI). MYC transcriptional activity was evaluated by RNA sequencing (RNA-seq) analysis of canonical MYC target genes. Results: The identified macrocyclic peptides exhibited potent antiproliferative activity against MYC-dependent tumor cells, with half-maximal inhibitory concentration (IC₅₀) values in the micromolar range. Fusion with the TAT peptide improved antiproliferative potency, yielding IC₅₀ values of 1–3 μM in MYC-dependent cell lines. BLI assays confirmed dose-dependent binding of the peptides to MYC, with dissociation constants (Kd) in the micromolar range. Furthermore, RNA-seq analysis revealed significant downregulation of canonical MYC target genes upon treatment with the TAT-fusion macrocyclic peptide, indicating specific suppression of MYC transcriptional activity. Conclusions: This work establishes the feasibility of using mRNA display to target the “undruggable” protein MYC and identifies a panel of macrocyclic peptides as promising lead candidates for further optimization toward targeted therapies for MYC-driven cancers. Full article

Background/Objectives: DNA-targeting small molecules that induce replication stress represent a promising strategy in anticancer drug development. 1,8-Naphthalimide (NI) derivatives are well-established DNA-intercalating agents, and heterocyclic annulation offers a rational approach to enhancing their potency and tumor selectivity. Here, we report the synthesis and biological evaluation of a novel series of benzofuran-containing naphthalimide derivatives, with particular focus on the lead dinitro-substituted compound 5d. Methods: Cytotoxic activity was assessed using the MTT assay in A549 (p53 wild-type), H1299 (p53-null), and MRC-5 cells. Long-term antiproliferative effects were evaluated by clonogenic survival assay. Cell cycle distribution was analyzed by propidium iodide staining and flow cytometry. Replication stress and DNA damage were quantified by EdU incorporation and γH2AX immunofluorescence, respectively. Apoptosis was assessed by Annexin V/PI staining and caspase-3/7 activation assay. p53 nuclear accumulation and autophagy induction were evaluated by immunofluorescence and Western blot, using LC3 as an autophagic marker. Results: All compounds exhibited cytotoxic activity in the nanomolar range, with 5d emerging as the most potent and selective. Clonogenic survival was significantly reduced, indicating durable suppression of proliferative capacity. Treatment with 5d induced G₁ arrest in A549 cells and the accumulation of H1299 cells in G₂/M, consistent with p53-dependent and p53-independent checkpoint activation, respectively. EdU incorporation was markedly reduced, while γH2AX intensity increased, collectively supporting a replication stress-driven mechanism of DNA damage. Apoptosis was confirmed by increased Annexin V-positive populations and caspase-3/7 activation. LC3 puncta formation and LC3-I/LC3-II conversion were increased, indicating LC3 processing and autophagosome accumulation consistent with the activation of autophagy-related processes. Conclusions: 5d induces a cellular phenotype consistent with replication stress, including reduced EdU incorporation, γH2AX accumulation, cell cycle arrest, and apoptotic cell death in a p53 status-dependent manner. These findings establish benzofuran-annulated naphthalimides as a promising scaffold for the development of anticancer agents that exploit replication stress vulnerabilities in tumor cells. Full article

Andean berry (Vaccinium meridionale Swartz) is an underutilized fruit that could serve as a source of bioactive compounds with biological properties associated with apoptosis and cytotoxicity in colorectal cancer cells. This study aimed to evaluate the cytotoxic and proapoptotic effects of Andean berry juice (ABJ) in human SW480 and SW620 colon cancer cell lines, which represent early-stage and metastatic colorectal cancer, respectively. The juice was prepared from freeze-dried fruits, and several concentrations were assayed in cells. Bioactive compounds in ABJ showed the strongest reductions in metabolic activity and proliferation observed in SW620 cells. ABJ treatments promoted early apoptosis while inducing cell cycle arrest in the S phase (SW480) and in the G2/M (SW620). Mild mitochondrial depolarization was observed, while increased reactive oxygen species (ROS) accumulation was detected in both cell lines. More proteins involved in the apoptotic process were modulated in SW620 cells, whereas SW480 displayed greater fold changes in regulatory and stress-response proteins. Proteomics and bioinformatics analyses suggested that extrinsic apoptosis predominated in SW480 cells, whereas intrinsic apoptosis was observed in SW620 cells. These results highlighted the cytotoxic and pro-apoptotic potential of the combined activity of polyphenolic compounds from ABJ, demonstrating distinct mechanisms in vitro. Full article

Melanoma exhibits pronounced metabolic plasticity and mitochondrial dependency, contributing to therapeutic resistance and tumor progression. Targeting mitochondrial function therefore represents a promising anticancer strategy. 2-Aminoethyl dihydrogen phosphate (2-AEH₂P), a bioactive phosphomonoester, has demonstrated antiproliferative potential, while metformin, a clinically established antidiabetic drug, acts as a mitochondrial complex I inhibitor and metabolic modulator. This study investigated the cytotoxic and mechanistic effects of 2-AEH₂P and metformin hydrochloride, individually and in combination, in human (SK-MEL-28) and murine (B16-F10) melanoma models, using non-tumorigenic fibroblasts (FN1 and L929) as controls. Cell viability, proliferation dynamics, cell-cycle distribution, mitochondrial membrane potential (ΔΨm), and apoptosis-associated markers were evaluated by flow cytometry. 2-AEH₂P reduced melanoma cell viability and proliferation while inducing G2/M accumulation, DNA fragmentation, mitochondrial depolarization, increased cytochrome c release, caspase-3 and caspase-8 activation, upregulation of p53 and Bad, and downregulation of Bcl-2. Metformin alone exerted moderate cytotoxic and pro-apoptotic effects. Notably, combined treatment markedly potentiated mitochondrial depolarization and intrinsic apoptotic signaling in melanoma cells, significantly lowering IC₅₀ values and enhancing caspase activation and cytochrome c release. Bliss independence analysis demonstrated synergistic interaction in SK-MEL-28 and B16-F10 cells. Although interaction scores indicated synergy in one fibroblast model, absolute cytotoxicity remained lower than in melanoma cells. These findings demonstrate that metabolic co-targeting with metformin enhances mitochondrial dysfunction-associated apoptotic signaling in melanoma cells, supporting a drug repositioning strategy aimed at exploiting mitochondrial vulnerability in metabolically adaptable tumors. Full article

Background/Objectives: Resistant pathogenic bacteria and fungi are a growing problem worldwide; therefore, the discovery of new active ingredients is an important challenge for which the functionalization of natural terpenes with biologically active heterocycles can provide a basis. To reach this goal, a series of 1,4-disubstituted-1,2,3-triazole conjugates was designed and synthesized starting from commercially available α-santonin. Methods: The key azido derivative intermediate was prepared according to literature procedures via Michael addition between dehydrosantonin and the TMSN₃/AcOH/Et₃N system at its highly reactive α-methylene-γ-lactone motif. Subsequently, the obtained azide was applied to regioselective Huisgen 1,3-dipolar cycloaddition reaction with a wide range of terminal alkynes bearing N-, S- and O-heterocycles. These include pyridine, pyrimidine, purine, quinoline, indol, or coumarin to afford the sesquiterpene–heterocycle chimaeras. All triazole conjugates were screened for in vitro antiproliferative activity by MTT assay against HeLa, MDA-MB231, SiHa, MCF-7 and A2780 human cancer cell lines compared with fibroblast cells (NIH/3T3) to check their cytotoxicity and antimicrobial effects on two Gram-positive (B. subtilis, S. aureus) pathogenic bacteria, two Gram-negative (E. coli and P. aeruginosa) pathogenic bacteria, and two yeasts (C. krusei and C. albicans). Results: The results indicated that most of the examined compounds expressed weak activity against human cell lines, while some of them showed moderate activity against S. aureus (up to 99% inhibition at 100 µg/mL conc.), C. krusei (up to 51% inhibition at 10 µg/mL conc.) and C. albicans (up to 52% inhibition at 10 µg/mL conc.). Conclusions: Further structural modification of the best, selective antibacterial and antifungal compounds may open the possibility to the development of effective natural sesquiterpene-based selective antimicrobial agents. Full article

Background: Instant Cascara (IC) beverages, derived from dried coffee cherry pulp, represent an upcycled plant-based ingredient rich in phenolic compounds and methylxanthines. Although spray-drying enables the production of soluble cascara powders without carriers, previous sensory evaluation highlighted limitations in palatability, supporting the need for formulation strategies. Objective: To evaluate how the incorporation of inulin-type carriers with different degrees of polymerization modulates production yield, the apparent recovery of bioactive compounds, and formulation-dependent in vitro biological and receptor-level responses of Instant Cascara beverages. Methods: Formulations without carrier (IC 0.0) and with long-chain inulin (IC 1.0) or oligofructose-enriched inulin (IC 2.0) were prepared and characterized. Production yield, phytochemical composition, and in vitro antioxidant, anti-inflammatory, antiproliferative, and receptor-mediated responses were assessed using analytical tools, cell-based assays, and receptor-based platforms. Results: Carrier incorporation improved production yield, particularly for IC 1.0. Although differences in apparent recovery of bioactive compounds were observed, all formulations preserved relevant in vitro biological activities. IC 2.0 showed stronger nitric oxide inhibition and apoptosis induction in colorectal cancer cell models. Receptor-based assays revealed formulation-dependent differences, including reduced activation of bitter taste receptors (TAS2Rs), absence of sweet receptor (TAS1R2/TAS1R3) activation, and modulation of muscarinic (M3) and dopaminergic (D3/D4) receptor responses. These effects are consistent with variations in the composition and effective concentration of bioactive compounds between formulations, particularly caffeine. Conclusions: The incorporation of inulin-type carriers influences production yield and modulates in vitro biological responses and receptor-level responses of Instant Cascara beverages. IC 2.0 represents a formulation with a favorable balance between technological performance and functional responses, associated with a distinct receptor-level profile. This balance may be related to a reduced contribution of bitterness-associated compounds, such as caffeine, together with the preservation of other bioactive components contributing to the observed biological responses. These findings provide a mechanistic in vitro basis for future sensory and in vivo studies evaluating how formulation-dependent differences in bioactive composition may influence physiological responses and consumer perception. Full article

Two new anthraquinone derivatives, (±)-1′-O-methyl-6-chloroaverantin (1a and 1b) and 6-chloroaverythrin (2), and one new diphenyl ether 1-((E)-but-2-en-2-yl)-3,8-dihydroxy-6-((E)-4-hydroxybut-2-en-2-yl)-4,9-dimethyl-11H-dibenzo[b,e][1,4]dioxepin-11-one (3), along with six known compounds, were isolated from the fungus Aspergillus sp. SCSIO 41331 collected from the deep-sea sediment in the cold-seep area of the South China Sea. Elucidation of planar structures was achieved via 1D and 2D NMR and mass spectrometry, whereas stereochemistry was validated through optical rotation and NOE correlations, chiral phase HPLC analysis and NMR calculation. All compounds were assessed for antitumor activity, among which compound 4 displayed moderate antiproliferative activity against HT29 cells and suppressed colony expansion. Full article

Epigallocatechin gallate (EGCG) is the major polyphenol in green tea and is frequently used in food supplements. In recent years, numerous studies have highlighted the bioactivity of polyphenols beyond their established role as radical scavengers. However, EGCG is highly unstable in slightly basic solutions such as cell culture medium. It therefore remains unclear whether the biological effects attributed to EGCG are caused by the parent compound itself or by its oxidation products, including the dimers examined here. In this study, the effects of EGCG focusing on apoptosis induction and histone deacetylases (HDAC) were compared with those of its major oxidation products, theasinensin A (TSA), theasinensin D (TSD), and oolongtheanin digallate (OTDG), in the human hepatocellular carcinoma cell line HepG2. The induction of cellular pathways involved in apoptosis was investigated using several in vitro biochemical approaches. Transcriptional analysis of apoptosis-associated genes revealed distinct expression profiles, and caspase activities were differentially affected by the test compounds. HDAC activity in nuclear protein extracts was significantly reduced after incubation with the stabilized oxidation products, whereas no comparable HDAC-inhibitory effect was observed after direct incubation of HepG2 cells. Nevertheless, HDAC gene expression, particularly of class I isoforms, was modulated by the test compounds in the low micromolar range. These effects diminished at concentrations associated with the onset of apoptosis. Furthermore, untargeted proteomics identified ribosomal proteins as additional cellular targets. Overall, these findings help to clarify the contribution of abundant EGCG oxidation products to the antiproliferative and HDAC modulating effects commonly attributed to the parent compound under cell culture conditions, underscoring the importance of investigating these oxidation products. Full article