Chemico-Biological Interactions最新文献

{"title":"Upregulation of ACHE and BACE2 genes by oleacein in Alzheimer's disease and neuroblastoma","authors":"Nicoletta Polerà ,&nbsp;Giada Juli ,&nbsp;Giuseppe Agapito ,&nbsp;Antonio Procopio ,&nbsp;Maria Lucibello ,&nbsp;Monica Nardi ,&nbsp;Sonia Bonacci ,&nbsp;Marianna Milano ,&nbsp;Mario Cannataro ,&nbsp;Dmitry Lim ,&nbsp;Emanuela Altomare ,&nbsp;Mariamena Arbitrio","doi":"10.1016/j.cbi.2026.111909","DOIUrl":"10.1016/j.cbi.2026.111909","url":null,"abstract":"<div><div>Alzheimer's disease (AD) and neuroblastoma are distinct conditions that affect the nervous system. However, they share some molecular similarities, particularly concerning the amyloid precursor protein (APP) and related pathways. While previous studies have demonstrated a correlation between neurodegenerative diseases and various tumors, the causality and direction of their relationship remain unclear. Oleacein, one of the most abundant polyphenols in Extra Vergin Olive Oil (EVOO) may exert neuroprotective and/or antitumor effects. In this study, we explored the effects of the polyphenol oleacein, obtained by a simple and efficient sustainable semi-synthesis starting from natural oleuropein, on AD-related genes in SHSY5Y, a human neuroblastoma cell line, and in 3Tg-iAstro cells, immortalized astrocytes from the hippocampus of 3xTg-AD mice, to identify potential shared biological pathways.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111909"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145953458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic kidney toxicity of polylactic acid nanoplastics and Cr(VI): Ferroptosis aggravated by mitophagy","authors":"Yuankun Zhou ,&nbsp;Jiajun Guo ,&nbsp;Xiaoyan Feng ,&nbsp;Hengyi Xu","doi":"10.1016/j.cbi.2026.111915","DOIUrl":"10.1016/j.cbi.2026.111915","url":null,"abstract":"<div><div>Nanoplastics (NPs) and chromium (Cr) are ubiquitous in the environment, causing severe pollution and posing significant potential threats to human health. Polylactic acid (PLA) and Cr are among widely used bioplastic and heavy metal, respectively, both capable of contaminating water sources through corresponding pathways and posing substantial risks to human health. Nanoplastics can act as carriers for heavy metals, thereby enhancing their bioaccumulation and toxicity. Therefore, this study investigated the effects of combined exposure to Cr(VI) and PLA NPs on mice kidneys and its potential mechanisms. Results indicated that exposure to PLA NPs alone did not exhibit significant toxic effects on the kidneys. However, combined exposure to Cr(VI) and PLA NPs caused severe kidney damage in mice. This indirectly suggests that Cr(VI) and PLA NPs exhibit synergistic toxicity rather than simple additive effects. Furthermore, combined exposure exacerbated the toxic mechanism by inducing mitochondrial damage and excessive reactive oxygen species (ROS) production, thereby triggering mitophagy. Overactivated mitophagy exacerbated lipid peroxidation by releasing free iron, thereby amplifying ROS-mediated ferroptosis. This study investigates the synergistic renal toxicity of Cr(VI) and PLA NPs, providing scientific evidence for the combined toxicity mechanism of exposure to MNPs and heavy metals.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111915"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Imiquimod-induced colitis: A novel ROS/ERK-driven model of intestinal inflammation and barrier dysfunction","authors":"Kuang-Ting Liu ,&nbsp;Shu-Hao Chang ,&nbsp;Kuan-Chen Wu ,&nbsp;Zheng-Yi Li ,&nbsp;Mao-Chia Chang ,&nbsp;Yen-Chu Huang ,&nbsp;Mu-Chi Chung ,&nbsp;Shih-Chung Wang ,&nbsp;Yi-Ju Chen ,&nbsp;Jeng-Jer Shieh","doi":"10.1016/j.cbi.2026.111907","DOIUrl":"10.1016/j.cbi.2026.111907","url":null,"abstract":"<div><div>Psoriasis and inflammatory bowel disease (IBD) are chronic immune-mediated disorders affecting the skin and gut, respectively, and share underlying mechanisms involving immune dysregulation and microbiota alterations. Imiquimod (IMQ), a compound commonly used to induce psoriasis-like skin inflammation in mice and exacerbate dextran sulfate sodium (DSS)-induced colitis. Accumulated research findings indicate that IMQ-induced reactive oxygen species (ROS) play a crucial role in biological functions and inflammation. In this study, we investigate the role of ROS in the pathogenesis of intestinal colitis and assess its potential as a therapeutic target by exposing mice to IMQ and establishing a novel disease model. Our results demonstrate that IMQ directly induces colitis-like inflammation in the intestines by depleting the mucus layer, reducing mucin 2 production, and increasing intestinal permeability. This induced model exhibits key features of inflammatory bowel disease, including pathological tissue characteristics. IMQ disrupts intestinal tight junctions and weakens barrier function, primarily through the ROS/extracellular signal-regulated kinase pathway. Moreover, antioxidant pretreatment alleviates colitis-like symptoms and restores intestinal barrier integrity. This IMQ-induced colitis model provides new insights into the molecular mechanisms underlying IBD and suggests its utility as a translational platform for assessing the therapeutic potential of redox-modulating interventions.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111907"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145924426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Biogenic Ag/AgCl nanocomposites induce apoptosis via mitochondrial pathway and reduce size of 3D HT29 colorectal cancer spheroids” [Chemico-Biological Interactions 421(2025) 111759]","authors":"Gokhan Gorgisen ,&nbsp;Cigdem Aydin Acar","doi":"10.1016/j.cbi.2026.111924","DOIUrl":"10.1016/j.cbi.2026.111924","url":null,"abstract":"","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111924"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental pyridinium disinfectants impair cortisol metabolism via 11β-hydroxysteroid dehydrogenase 2 inhibition: A cross-species risk evaluation","authors":"Chaochao Gong ,&nbsp;Xiuzhi Zhang ,&nbsp;Yu Zhang ,&nbsp;Xishi Chen ,&nbsp;Hao Lin ,&nbsp;Ren-shan Ge ,&nbsp;Youming Zhao","doi":"10.1016/j.cbi.2026.111914","DOIUrl":"10.1016/j.cbi.2026.111914","url":null,"abstract":"<div><div>11β-Hydroxysteroid dehydrogenase type 2 (11β-HSD2), a key enzyme in glucocorticoid inactivation, is expressed in human and rat placentas and kidneys. However, the inhibitory effects of alkyl (C1–C20) pyridinium quaternary ammonium disinfectants (PYRs) on 11β-HSD2 remain unexplored. This study evaluated PYRs through inhibitory potency assays, mechanistic investigations, structure-activity relationship (SAR)/3D-QSAR modeling, and molecular docking using human and rat 11β-HSD2 enzymes. Human 11β-HSD2 inhibition by PYRs followed a distinct V-shaped trend: potency increased from C12 to C16 (IC₅₀: C12 = 132.81 μM, C14 = 19.62 μM, C16 = 1.96 μM) but declined beyond C16 (C18 = 14.45 μM, C20 = 100.76 μM). Shorter-chain PYRs (C1–C8) were inactive at ≤100 μM. Rat 11β-HSD2 exhibited a similar inhibition pattern. SPR analysis revealed that C16 displayed the highest binding affinity (<em>KD</em> = 1.98 μM) with human 11β-HSD2. Mechanistic analysis revealed mixed/noncompetitive inhibition, with PYRs binding both the free enzyme and enzyme-substrate complex. In BeWo cells, C12–C20 PYRs inhibited cortisol metabolism at 10–100 μM, whereas C16 was effective at ≥1 μM. Molecular docking indicated PYRs interact with the NAD ⁺ binding site in both species. SAR analysis identified lipophilicity, steric bulk, and flexibility as critical inhibitory determinants, with higher values enhancing potency. A 3D-QSAR pharmacophore model confirmed hydrophobic interactions as essential for inhibition. Notably, species-specific binding differences suggest caution when extrapolating rodent data to humans. These findings highlight the endocrine-disrupting potential of PYRs, demonstrating their structure- and species-dependent interference with cortisol metabolism, with implications for chemical safety assessment.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111914"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145986150","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A single cell transcriptomics-based analysis provides mechanistic insights into the chronic low-concentration effects on hematopoietic disruption in zebrafish(Danio rerio) by Antinomy","authors":"Yuanyi Sun ,&nbsp;Zhongqian Cen ,&nbsp;Shirui Liu ,&nbsp;Aijiang Yang ,&nbsp;Jingyun Zhang ,&nbsp;Qing Li ,&nbsp;Xia Hu ,&nbsp;Zhengting Hou","doi":"10.1016/j.cbi.2025.111892","DOIUrl":"10.1016/j.cbi.2025.111892","url":null,"abstract":"<div><div>Antimony (Sb), a widely used strategic metal, has raised growing concerns due to its environmental persistence and potential toxicity. However, the chronic effects of low-level Sb exposure on hematopoietic function remain poorly understood. In this study, zebrafish (<em>Danio rerio</em>) were exposed to Sb at concentrations of 0, 5, 50, 500, and 5000 μg/L for 28 days to investigate the hematotoxic effects and underlying mechanisms. Biochemical assays revealed that Sb exposure significantly disrupted blood glucose and lipid metabolism, reduced glucose levels, and altered lipid profiles in a concentration-dependent manner. In addition, Sb exposure increased cytokines such as NFAT, M-CSF, and IL-11. Histopathology revealed pronounced damage to the kidney, the primary hematopoietic organ in zebrafish. Single-cell RNA sequencing identified 13 hematopoietic cell populations. Differentially expressed genes were significantly enriched in the IL-17 pathway, with downstream activation of NF-κB and increased expression of TNF-α and MMP-9. These findings provide mechanistic insights into Sb-induced hematopoietic imbalance and renal injury, highlighting the role of IL-17-mediated inflammatory responses in mediating Sb toxicity. Overall, this study offers a valuable reference for ecological risk assessment and health hazard evaluation of Sb contamination.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111892"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949534","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Polycyclic aromatic hydrocarbons-induced suppression of the PPARα/ACAA1 axis drives hepatic steatosis: Integrating epidemiology, network toxicology, and experimental validation","authors":"Haonan Cui ,&nbsp;Peng Zou ,&nbsp;Wang Yang ,&nbsp;Shijun He ,&nbsp;Jinyuan Shi ,&nbsp;Ting Sun ,&nbsp;Mengge Wang ,&nbsp;Zhiyong Song ,&nbsp;Hanni Guan ,&nbsp;Tong Wang ,&nbsp;Lei Sun ,&nbsp;Qing Chen ,&nbsp;Jinyi Liu ,&nbsp;Xi Ling ,&nbsp;Jia Cao ,&nbsp;Lin Ao","doi":"10.1016/j.cbi.2026.111923","DOIUrl":"10.1016/j.cbi.2026.111923","url":null,"abstract":"<div><h3>Background</h3><div>Non-alcoholic fatty liver disease (NAFLD) is a common liver condition linked to chronic hepatic dysfunction and systemic metabolic disorders. Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous and persistent environmental pollutants associated with the pathogenesis of non-alcoholic fatty liver disease (NAFLD). However, underlying molecular mechanisms linking PAH exposure to hepatic steatosis remain incompletely elucidated.</div></div><div><h3>Objectives</h3><div>This study aimed to clarify the association between PAHs exposure and NAFLD and unravel the core molecular pathways driving PAHs-induced hepatic lipid metabolism dysfunction.</div></div><div><h3>Methods</h3><div>Cross-sectional analyses were performed using data from the 2007–2016 National Health and Nutrition Examination Survey (NHANES) to investigate the associations of urinary PAH metabolites with NAFLD prevalence, hepatic steatosis index (HSI), and serum metabolic indicators. The relationships between PAHs and metabolic indicators were further validated in participants from the Preconception Reproductive Health and Birth Outcome Cohort (PREBIC). We then integrated network toxicology, bioinformatics, and both in vivo and in vitro models to elucidate the molecular pathways through which benzo[a]pyrene (BaP), a prototype PAHs, drives hepatic steatosis.</div></div><div><h3>Results</h3><div>Analyses of NHANES data revealed significant positive associations between PAHs exposure and NAFLD incidence, the hepatic steatosis index (HSI), and serum triglyceride (TG) level. Validation in the PREBIC cohort consistently confirmed the robust association between PAHs exposure and increased TG level. Elevated serum TG levels emerged as a key metabolic indictor of PAHs-induced hepatic steatosis. Network toxicology revealed that PPARα is a key molecular involved in lipid metabolism disruption by BaP, contributing to NAFLD. Integrated bioinformatics analyses further revealed that the binding of BaP to PPARα represses the expression of the downstream gene ACAA1. In vivo and in vitro experiments confirmed that BaP inhibits PPARα signaling, impairing peroxisomal function and fatty acid degradation and thus, leadings to hepatic lipid accumulation.</div></div><div><h3>Conclusion</h3><div>PAHs exposure is associated with hepatic steatosis and elevated serum TG level, and PPARα/ACAA1 axis suppression constitutes a key pathway through which BaP disrupts hepatic lipid metabolism. This study provides novel insights into the environmental etiology of NAFLD and identifies the PPARα/ACAA1 axis as a potential therapeutic target for PAHs-related NAFLD.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111923"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992351","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alisol B 23-acetate as a promising natural bioactive tetracyclic triterpenoid: A review of its extraction methods, pharmacokinetics, metabolism, pharmacology, and toxicity","authors":"Yinqi Wu ,&nbsp;Yu Du ,&nbsp;Zhichen Wang ,&nbsp;Yi Wu ,&nbsp;Zhen Li ,&nbsp;Aimin Wang ,&nbsp;Yuran Sun","doi":"10.1016/j.cbi.2026.111928","DOIUrl":"10.1016/j.cbi.2026.111928","url":null,"abstract":"<div><div>Natural compounds are increasingly gaining attention in modern pharmaceutical research due to their multiple therapeutic effects and low toxicity. Alisol B 23-acetate (AB23A), a naturally derived triterpenoid compound isolated from <em>Alisma orientale</em>(AO), exhibits a variety of pharmacological activities. It demonstrates significant therapeutic potential in the treatment of chronic atherosclerosis, anti-inflammatory responses, liver and kidney protection, as well as anticancer effects. Moreover, its low toxicity and high safety profile make it an attractive compound for researchers. This suggests that AB23A is a promising natural compound with substantial development potential. In this review, we systematically reviewed the extraction methods, pharmacokinetics, metabolism, pharmacology, and toxicity of AB23A. Additionally, the current research status of AB23A was comprehensively analyzed and summarized, providing valuable reference materials for further investigation and drug development.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111928"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aryl hydrocarbon receptor pathway mediates cigarette smoke-induced skin inflammation and sebaceous gland hyperplasia","authors":"Ying Xie ,&nbsp;Aoyin Liu ,&nbsp;Junqi Bai ,&nbsp;Baoling Xie ,&nbsp;Hankun Chen ,&nbsp;Yirui Liu ,&nbsp;Xian Zhang ,&nbsp;Wei Zhu","doi":"10.1016/j.cbi.2026.111930","DOIUrl":"10.1016/j.cbi.2026.111930","url":null,"abstract":"<div><div>Cigarette smoke (CS) represents a major exogenous stimulus associated with various skin pathologies, yet the precise mechanisms driving skin inflammation and glandular dysfunction remain incompletely elucidated. The aryl hydrocarbon receptor (AhR) is a transcription factor involved in various cellular functions, though its role in skin is unclear. This study investigates how cigarette smoke extract (CSE) mediates skin inflammation and abnormal glandular hyperplasia via AhR activation. In a CS-exposed mouse model, histopathological staining revealed that CS exposure induced inflammatory cell infiltration, mast cell degranulation and increased sebaceous gland cells. Immunohistochemistry showed higher levels of CD68, lymphocyte antigen 6 family member G (Ly-6G), and AhR, along with increased mRNA expression of inflammatory cytokines such as interleukin-1β (IL-1β) and interleukin-6 (IL-6). Integrated network toxicology and transcriptomics suggested that nicotine derivatives, indoles, and bipyridyl components in CSE activate the AhR complex, increasing cytochromes P450 family 1 (CYP1) subfamily A member 1 (CYP1A1), CYP1B1, and glutathione S-transferase (GST), while promoting the release of inflammatory mediators. Co-culture experiments with 3T3-L1 preadipocytes and RAW264.7 macrophages indicated that CSE-treated macrophages enhance adipocyte proliferation and lipid accumulation via paracrine signaling. In summary, CS exposure activates the AhR pathway, leading to increased inflammation and sebaceous gland cell proliferation, which collectively contribute to inflammatory infiltration, sebaceous gland hyperplasia, and collagen remodeling in skin tissue. These findings offer deeper theoretical insights for preventing and treating CS-related skin diseases.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111930"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146004705","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The in vitro assessment of the prooxidative action of the novel aroylacrylic acid phenylamides in A549 and MCF7 cancer cell lines","authors":"Snežana K. Bjelogrlić ,&nbsp;Tamara Vujatović-Velimirov ,&nbsp;Aleksandra Korać ,&nbsp;Sara Stojanović ,&nbsp;Jelena Grahovac ,&nbsp;Maja D. Vitorović-Todorović","doi":"10.1016/j.cbi.2026.111925","DOIUrl":"10.1016/j.cbi.2026.111925","url":null,"abstract":"<div><div>Aroylacrylic acids, their phenylamides and other analogues bearing structural scaffold comprising of the two phenyl rings linked by three or four carbon atoms exert prominent anticancer activity. To unravel the relying mechanism responsible for induction of cell death by aroylacrylic acid phenylamides, we designed four novel structural analogues (<strong>1a</strong>-<strong>1d</strong>) by means of Michaels’ addition of secondary cyclic amines to aroylacrylic acid phenylamides. A battery of biological assays has been utilized to evaluate functional and morphological alterations triggered by the investigated treatments in A549 and MCF7 cell lines that are KRAS^mut and KRAS^wt, respectively, using carbonyl cyanide-<em>p</em>-trifluoromethoxyphenylhydrazone as a positive control. Concomitant treatment with, <em>N</em>-acetylcysteine reversed cell death response induced by investigated compounds (75.7 ± 15.1 % and 33.1 ± 9.9 % in average for MCF7 and A549 cells, respectively), suggesting that the generation of reactive oxidative species (ROS) was the key trigger of the cell death. Moreover, MCF7 cells were more susceptible to experimental treatments than A549 cells, whereas examination of the mitochondrial membrane potential and superoxide generation showed that the integrity of mitochondria in MCF7 cell line was devastated quickly after exposure to the investigated compounds. As KRAS^mut A549 cells have dysfunctional oxidative phosphorylation (OXPHOS), these results imply that the fully operative OXPHOS in KRAS^wt cells exceedingly amplified ROS production upon treatment. Additionally, ultrastructural analysis confirmed significant mitochondrial damage in both cell lines. Investigated compounds potently disrupt mitochondrial function and can serve as a valuable asset for testing capacity of new antioxidant agents.</div></div>","PeriodicalId":274,"journal":{"name":"Chemico-Biological Interactions","volume":"426 ","pages":"Article 111925"},"PeriodicalIF":5.4,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}