Toxicology Research最新文献

{"title":"Response.","authors":"Hülya Tezel Yalçın, Deniz Arca Çakır, Anıl Yirün, Sonia Sanajou, Gözde Işık, Özlem Bozdemir, İbrahim Özçelik, Merve Güdül Bacanlı, Naciye Dilara Zeybek, Terken Baydar, Pınar Erkekoğlu","doi":"10.1093/toxres/tfaf126","DOIUrl":"10.1093/toxres/tfaf126","url":null,"abstract":"","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 5","pages":"tfaf126"},"PeriodicalIF":2.9,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12448389/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111627","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective effects of <i>Melissa officinalis</i> against Chlorpyrifos-induced hepatotoxicity in rat: a dose-dependent evaluation of biochemical, histological, and oxidative stress markers.","authors":"Fatemeh Alijaniha, Fatemeh Emadi, Zahra Bahaeddin, Mohsen Naseri, Mahya Motie Nasrabadi, Maliheh Soodi","doi":"10.1093/toxres/tfaf114","DOIUrl":"10.1093/toxres/tfaf114","url":null,"abstract":"<p><p>Chlorpyrifos (CPF) is a widely used pesticide known for its hepatotoxic effects. <i>Melissa officinalis L.</i> is a medicinal herb, recognized in Persian medicine for its diverse biological activities and protective effects against poisons<i>.</i> This study aimed to study the protective effects of <i>M. officinalis</i> against CPF-induced hepatotoxicity in male rats. Experimental groups included control, sham, CPF (10 mg/kg), <i>M. officinalis</i> (500 mg/kg), and combinations of CPF with <i>M. officinalis</i> (100, 250, and 500 mg/kg). <i>M. officinalis</i> dried powder was administered orally for four weeks, with CPF introduced in the third week. Following treatment, biochemical parameters include serum levels of AST, ALT, ALP, LDH, oxidative stress in liver tissue, acetylcholinesterase (AChE) activity and paraoxonase-1 (PON) activity in the serum, and PON1 gene expression in the liver, along with histological alterations in liver tissue were assessed. Results indicated that CPF-treated groups had significantly increased AST, ALT, and LDH levels in serum and induced oxidative stress in liver tissue, while <i>M. officinalis</i> ameliorate these changes in a dose-dependent manner. Histological analysis showed <i>M. officinalis</i> at 250 mg/kg dose prevented CHF-induced inflammation and degeneration in the liver, but the 500 mg/kg dose resulted in cytoplasmic vesicle lesions and inflammatory cell infiltration. AChE activity was significantly inhibited by CPF, and <i>M. officinalis</i> did not mitigate this inhibition. PON activity and gene expression were also unaffected by <i>M. officinalis</i> treatment. In conclusion, <i>M. officinalis</i> effectively mitigated CPF-induced liver damage and oxidative stress at low to medium doses, while higher doses caused tissue damage.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 5","pages":"tfaf114"},"PeriodicalIF":2.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12418947/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Examination of the effects of polyunsaturated fatty acids on the alzheimer model caused by amiloid β_1-42 toxicity in human SHSY5Y cells by in vitro methods.","authors":"Mualla Pınar Elci, Sema Ören, Ece Miser-Salihoglu, Sevgi Yardim-Akaydin","doi":"10.1093/toxres/tfaf130","DOIUrl":"10.1093/toxres/tfaf130","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive, chronic disease characterized by impaired cognitive function. Currently, there is no complete cure for ad; current treatments are aimed at reducing symptoms and slowing the progression of the disease. It is thought that the amount of fatty acid consumption and the balance between them may be protective against neurological diseases. In this study, it was aimed to determine the protective effects of Ω3/Ω6 polyunsaturated fatty acids ratios in Aβ_1-42-induced ad model in human neuroblastoma (SH-SY5Y) cells. The viability of cells was determined by MTT assay. The percentage of apoptotic cells was determined by FITC-conjugated Annexin-V/PI. ROS, MMP and cell cycle analysis were performed by flow cytometry. The amount of acetylcholinesterase enzyme was measured with a commercial kit. 48 h after the application, a statistically significant decrease was observed in the MTT test in the 1/1, 1/2 and 1/8 groups and in the amount of AChE in the 1/4, 1/8 and 1/16 groups. According to apoptosis findings, all ratios were observed to reduce cell viability compared to the control group. ROS and MMP levels were detected to decrease in all groups compared to the control group. The highest neuroprotective effect against oxidative stress was observed at 1/1 dose. Aβ_1-42 induced blockade of the cell cycle was observed to be partially corrected by 1/8 dose. As a result, it can be said that Ω6 and Ω3 fatty acids, when used in 1/4 and 1/8 doses can provide a protective effect against Alzheimer's disease.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf130"},"PeriodicalIF":2.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392398/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MiR-1291 mediates the protective effect of sevoflurane preconditioning against hypoxia/reoxygenation-induced myocardial cell injury.","authors":"Jingyi Shi, Shaoke Hou, Xinyu Yao","doi":"10.1093/toxres/tfaf122","DOIUrl":"10.1093/toxres/tfaf122","url":null,"abstract":"<p><p>The protective effects of sevoflurane (Sev) in cardiovascular disease have been well documented in studies. The investigation aimed to clarify the contribution of miR-1291 to the pathophysiological process of hypoxia-reoxygenation (H/R)-induced cardiomyocyte injury in the setting of Sev preconditioning. H/R cell models were constructed with AC16 cells and the cell models were pretreated with 1%, 1.5% and 2% concentrations of Sev. Quantitative reverse transcription polymerase chain reaction was performed to detect miR-1291 and NF2 expression in cells. Cell viability was assessed using the cell counting kit-8 assay. Apoptosis was evaluated via flow cytometry. Cellular cardiac troponin I (cTnI), lactate dehydrogenase (LDH), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels were detected by enzyme-linked immunosorbent assay. Dual luciferase reporter gene assay and RIP analysis were applied to validate the binding of miR-1291 to NF2. In the H/R cell model, miR-1291 was downregulated, and this was accompanied by reduced cell viability, increased apoptosis, and elevated levels of cTnI, LDH, IL-6 and TNF-α. In contrast, inhibition of miR-1291 expression impaired the protective effect of Sev on cardiomyocytes. NF2 was a downstream target gene of miR-1291, and miR-1291 negatively regulated the expression of NF2. Knockdown of NF2 expression alleviated the effects of miR-1291 inhibition on Sev-treated cells. Sev attenuates H/R-induced cardiomyocyte injury by regulating miR-1291/NF2 expression and inhibiting apoptosis and inflammatory responses. This study unveils a novel mechanism of Sev-mediated myocardial protection, offering theoretical support and potential therapeutic targets for myocardial injury prevention and treatment.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf122"},"PeriodicalIF":2.9,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12392403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936272","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Counteracting effects of Ethanolic extract of <i>allium Sativum</i> on Perfluorooctanoic acid-induced cardiotoxicity: insights into Keap1-Nrf2/PPARα pathways.","authors":"Eman El-Sayed Khayal, Hend S Eisa, Marwa Ahmed Abass, Shaimaa A Abdelrhman, Samar Sakr","doi":"10.1093/toxres/tfaf129","DOIUrl":"10.1093/toxres/tfaf129","url":null,"abstract":"<p><p>Perfluorooctanoic acid (PFOA) is a synthetic chemical belonging to per and poly-fluoroalkyl substances. It persists in the environment and accumulates in human bodies, leading to significant health concerns. <i>Allium sativum</i> (garlic) is acknowledged for its nutritional and anti-oxidative properties. Current research investigated the efficacy of <i>A. sativum</i> ethanolic extract against PFOA-induced cardiotoxicity. Fifty adult albino rats were grouped equally into five groups: control, vehicle, <i>A. sativum</i> (300 mg/kg), PFOA (25 mg/kg), and PFOA and <i>A. sativum</i>. Rats were daily gavaged with treatments for 8 weeks. Serum samples were used for measuring lactate dehydrogenase (LDH), total cholesterol, and triglycerides (TG) levels. Cardiac tissues were used for assessing oxidative stress biomarkers (heme oxygenase1 (HO1), catalase (CAT), superoxide dismutase (SOD), and malondialdehyde (MDA)), and nuclear Factor kappa-light-chain-enhancer of activated B cells (NF-κB). Also, the gene expression for nuclear factor erythroid-derived 2-like 2 (Nrf2), Kelch-like ECH-associated protein1 (Keap1), and peroxisome proliferator-activated receptor α (PPAR α) was determined. Cardiac tissues had undergone histopathological and immunohistochemical examination for caspase-3. Results revealed that PFOA exposure decreased the anti-oxidant enzymes (HO1, CAT, SOD), and markedly elevated levels of both MDA and NF-κB. PFOA inhibited the Nrf2 pathway as presented by the downregulated Nrf2 and upregulated Keap1 genes. Additionally, PFOA disturbed lipid metabolism via PPAR α downregulation. These changes were supported by histopathological changes and increased caspase-3 immunoexpression. A combination of <i>A. sativum</i> extract with PFOA provided significant protection against the aforementioned changes. Results suggested that <i>A. sativum</i> is an effective natural product that can attenuate PFOA-induced cardiotoxicity.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf129"},"PeriodicalIF":2.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381759/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936812","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LPS mediated neuronal c-Fos activation: whole-brain mapping, site and time effect in intoxicated mice.","authors":"Mona N Hussein, Khalid S Alotaibi, Saed A Althobaiti, Shatha B Albattal, Xiao Ke, Jinxia Dai, Gang Cao, Mohamed Mohamed Soliman","doi":"10.1093/toxres/tfaf131","DOIUrl":"10.1093/toxres/tfaf131","url":null,"abstract":"<p><p>Lipopolysaccharide (LPS; a bacterial endotoxin) treatment causes acute inflammatory conditions. Acute inflammation causes the brain to activate neurons in some brain nuclei known as circumventricular organs. The c-Fos immunoreaction could be used to assess this neural activity. The current study aimed to check the activated neurons in time and site effect during toxicity and inflammation induced by LPS. The c-Fos antibody immunofluorescence labeling was checked at one, three, and six hours after LPS intoxication. Moreover, a retrograde viral tracing approach was employed to verify the neuronal connections among certain brain nuclei that were activated. The results indicated the activation of several brain nuclei in the hippocampus, epithalamus, thalamus, hypothalamus, basal ganglia, midbrain, and medulla oblongata. The type of brain nuclei and the number of neurons that were activated in relation to the duration of acute inflammation were clearly different. Furthermore, this research demonstrated that these active brain nuclei were connected neuronally. Ultimately, acute inflammatory responses induced by LPS treatment activated dorsal raphe serotonergic neurons. Twenty-two brain nuclei were shown to be involved in the neuroinflammatory response via whole-brain mapping. One hour after LPS administration, neurons in the dorsomedial hypothalamic nucleus (DM), lateral septal nucleus (LS), and solitary tract nucleus (SOL) were significantly activated. However, the sensory circumventricular organs (CVOs) were activated three hours after LPS treatment. It was also demonstrated that dorsal raphe serotonergic neurons play a vital role in the body's reaction to acute inflammation. This study confirmed the involvement of dorsal raphe serotonergic neurons in response to acute inflammation and toxicity induced by LPS.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf131"},"PeriodicalIF":2.9,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12381757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Flumetralin based plant growth regulator used in tobacco cultivation induces immune and cytotoxicity in vitro.","authors":"Aline Mocellin Conte, Fernanda Mocellin Conte, Larissa V Cestonaro, Maria Fernanda Nunes Ribeiro, Rodrigo F da Silva, Renata De Faveri, Larissa Benvenutti, Solange C Garcia, José Roberto Santin, Rodrigo Ligabue-Braun, Bruno Dutra Arbo, Marcelo Dutra Arbo","doi":"10.1093/toxres/tfaf118","DOIUrl":"10.1093/toxres/tfaf118","url":null,"abstract":"<p><p>Tobacco production lasts about 10 months and various pesticides are used, including growth inhibitors, which flumetralin is the most used. This is an herbicide that acts as a synthetic and plant growth regulator. Therefore, this work aimed to evaluate the toxicity of the growth regulator flumetralin in RAW 264.7 and 3T3 cell lines. Cytotoxicity was assessed by MTT reduction and neutral red uptake assays after 24 h of incubation with flumetralin. Mitochondrial integrity, production of reactive species and cytokine profile were evaluated in both cell lines. Furthermore, NO production was evaluated in RAW 264.7 cells, while comet assay was evaluated in 3T3 cells. An increase in reactive species production was observed in both cell lines. In RAW 264.7 cells were observed an increase in mitochondrial membrane potential, while 3T3 cells presented a mitochondrial depolarization. At all tested concentrations, flumetralin increased TNF-α levels and decreased IL-10 levels in RAW 264.7, and increased TNF and IL-1ß in 3T3 cells. In addition, at all tested concentrations, flumetralin induced DNA damage in 3T3 cells. It was possible to observe the cytotoxic effect of flumetralin on the tested cell lines, as well as a possible generation of an inflammatory response and immune deregulation.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf118"},"PeriodicalIF":2.9,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12371405/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis, in-vitro, <i>in-silico</i>, and global DNA methylation studies of curcumin-benzoquinone analog in triple-negative breast cancer (TNBC) cells.","authors":"Başak Günçer, Funda Özkök, Ebru Hacıosmanoğlu Aldoğan, Yasemin Oyacı, Esra Nazlıgül, Bilge Özerman Edis, Sama Akbarzadeh, Nihal Onul, Atilla Akdemir, Vildan Enisoğlu Atalay, Sacide Pehlivan","doi":"10.1093/toxres/tfaf128","DOIUrl":"10.1093/toxres/tfaf128","url":null,"abstract":"<p><p>Curcumin is a well-known anticancer agent used for many malignancies; however, its low bioavailability and solubility limit its use in clinical applications. To enhance its efficacy, we synthesized a novel curcumin-benzoquinone analog, JWB1 (3), and evaluated its anticancer potential against triple-negative breast cancer (TNBC) in vitro. We designed JWB1 (3) and structurally identified it using NMR, FTIR, MS, and UV-Vis techniques. The MTT assay was used to evaluate JWB1 (3) cytotoxicity in the MDA-MB-231, MCF-7, and HUVEC cell lines. Flow cytometry was used to examine apoptotic activation and reactive oxygen species (ROS) levels. Global DNA methylation was measured using an ELISA kit. Docking studies and molecular dynamics simulations revealed potential JWB1 (3) interactions with double-stranded DNA (dsDNA). JWB1 (3) showed selective cytotoxicity towards MDA-MB-231 cells (IC₅₀: 2.94 μg/mL, SI: 23.5 in 24 h), with minimal effects on HUVECs. Treatment with 10 μg/mL JWB1 (3) increased global DNA methylation levels in MDA-MB-231 cells (from 0.87% to 1.92%) more than in MCF-7 cells. The apoptosis assay showed that JWB1 (3) significantly induced MDA-MB-231 cells in the early apoptosis phase (early apoptosis: 45.65% vs. 2.95% in the controls). Furthermore, post-treatment, cancer cells showed a notable decrease in ROS levels. Supported by 100 ns molecular dynamics simulation, molecular docking investigations also showed a stable 3D structure and intercalation of JWB1 (3) with DNA. These findings imply that JWB1 (3) has notable anticancer potential against TNBC by inducing apoptosis, epigenetic modification, and DNA interaction.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf128"},"PeriodicalIF":2.1,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365976/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cigarette smoke impairs the endocytotic process in <i>Saccharomyces cerevisiae</i>.","authors":"Aditya Shukla, Srimonti Sarkar, Alok Kumar Sil","doi":"10.1093/toxres/tfaf127","DOIUrl":"10.1093/toxres/tfaf127","url":null,"abstract":"<p><p>The accumulation of misfolded proteins inside the cells has been considered to be an important contributor to the development of cigarette smoke-mediated diseases. Since endocytosis plays a crucial role in protein trafficking and clearance, impaired endocytosis may contribute to cigarette smoke-mediated protein accumulation. Therefore, the current study investigated the effects of cigarette smoke extract (CSE) on the endocytosis process in the yeast <i>Saccharomyces cerevisiae</i>. The current study demonstrated that treatment of cells with CSE resulted in reduced uptake of the FM4-64 stain, indicating impaired endocytosis. Further analysis revealed that CSE treatment resulted in a defect in the recruitment of proteins involved in endocytosis. Also, aberrant actin filament morphology was found upon CSE treatment, which might interfere with vesicle budding from the membrane. Moreover, the current study showed that the PI(4,5)P2 level in the plasma membrane in CSE-treated cells is reduced due to the failed translocation of MSS4 kinase to the membrane. This reduced PI(4,5)P2 results in aberrant actin filament morphology. Thus, the current study demonstrates that CSE treatment causes endocytosis defects and provides insight into this defective process.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf127"},"PeriodicalIF":2.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365969/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tanshinone IIA promotes METTL3/METTL14-mediated FDX1 m6A modification to induce cuproptosis in bladder cancer.","authors":"Bo Yang, Mengyuan Pan, Tianyi Tao, Kang Chen, Dehui Kong, Jidong Hao, Guoqiang Liao, Feng Liu, Hua Gong","doi":"10.1093/toxres/tfaf123","DOIUrl":"10.1093/toxres/tfaf123","url":null,"abstract":"<p><p>Tanshinone IIA (Tan IIA), a pleiotropic bioactive natural compound, has a general anti-tumor effect, as well as in bladder cancer. However, little is known about its mechanism. This work attempts to explore the mechanism of Tan IIA promoting cuproptosis in bladder cancer cells and the effective targets. Copper concentration and total m6A quantification were determined using test kits. Cell viability was tested by CCK-8. Gene expression was evaluated by western blot or qRT-PCR. The m6A methylation level of FDX1 was detected by methylated RNA immunoprecipitation. FDX1 3'UTR activity was evaluated by luciferase activity assay. YTHDC1 binding to FDX1 was detected by RNA immunoprecipitation assay. Inhibition of tumor growth by Tan IIA was verified using a mouse xenograft tumor model. Tan IIA inhibits cell viability and induces the expression of FDX1 and lip-DLAT, key regulators of cuproptosis, in bladder cancer cells. The copper chelator tetrathiomolybdate weakens the inhibiting effect of Tan IIA on cell viability; while Tan IIA enhances the inhibiting effect of elesclomol-Cu on cell viability. FDX1 knockdown reverses Tan IIA-induced cuproptosis. Tan IIA increases FDX1 m6A modification, which is reversed by S-adenosylhomocysteine, an inhibitor of METTL3/METTL14, and this event mediates Tan IIA-induced cuproptosis of bladder cancer cells. The effectiveness of SAH in Tan IIA promoting cuproptosis and antitumor utility is demonstrated in a xenograft tumor model. Tan IIA exerts an anti-bladder cancer effect by promoting the cuproptosis of tumor cells, and the possible mechanism is to promote the expression of FDX1 by METTL3/METTL14-mediated the increasing FDX1 m6A modification.</p>","PeriodicalId":105,"journal":{"name":"Toxicology Research","volume":"14 4","pages":"tfaf123"},"PeriodicalIF":2.9,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144936316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}