Molecular & Cellular Toxicology最新文献

{"title":"Toxicological implications of storage conditions on yeast vacuole properties and activities","authors":"Hyo Jin Choi, Taehwan Kim, Woo-Ri Shin, Jin-Pyo Lee, Uyen Le Ngoc Phuong, Ji-Young Ahn, Yang-Hoon Kim, Jiho Min","doi":"10.1007/s13273-024-00439-5","DOIUrl":"https://doi.org/10.1007/s13273-024-00439-5","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Yeast vacuoles, with their multifaceted functions, have been widely employed in various studies due to the versatility conferred by the diverse array of hydrolases contained within them. These enzymes exhibit non-specific enzymatic properties, enabling a broad spectrum of applications. However, the existing literature often neglects the critical aspect of vacuole storage conditions. To augment the utility of vacuoles, it is imperative to optimize their storage conditions.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study aims to comprehensively investigate the structural and functional changes occurring in vacuoles under varying storage conditions, with a particular emphasis on their relevance to toxicological aspects. Notably, we explore the pronounced structural alterations that accompany extended storage durations post-extraction.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Extended storage periods are found to be correlated with notable increases in vacuole size and a reduction in structural stability. Additionally, our examination of enzyme activity reveals a substantial upregulation of protease activity in vacuoles stored for 10 days post-extraction.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>These findings underscore the importance of appropriate storage methods for vacuoles, particularly in the context of their potential as valuable materials that efficiently harness their antibacterial and anticancer properties, while also shedding light on their toxicological implications in the field of cellular toxicology.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"63 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140635644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cobrotoxin, a single peptide from snake venom, ameliorates atopic dermatitis via suppression of MK2 modulated by IgE and IL-33","authors":"Jin Woo Lee, Younghoon Choi, Sang Heon Lee, No-June Park, Mediana Hadiwidjaja, Young Chang Sohn, Nurul Farhana Jufri, Eun-Hwa Sohn, Su-Nam Kim","doi":"10.1007/s13273-024-00442-w","DOIUrl":"https://doi.org/10.1007/s13273-024-00442-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease, causing significant impairment in daily life. It typically results from the compromised skin barriers and induces the Th2-dominant immune responses, which is heavily influenced by Interleukin-33 (IL-33). Meanwhile, snake venom has been known to be effective for various medical treatments. But, its role and mechanism in AD treatment are yet to be explored.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study aimed to explore the therapeutic potential of cobrotoxin (CoTX), a single peptide from snake venom, in treating allergic AD via in vitro and in vivo models.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Purified CoTX inhibited degranulation in RBL-2H3 cells, a marker for allergic inflammation. It reduced IgE secretion from B cells and modulated IL-33 expression in keratinocytes. CoTX effectively regulated both allergic and pseudoallergic pathways, suggesting its suppressive control over early and late stages of allergic reactions. The study also investigated CoTX’s impact on the IL-33 receptor ST2 and associated signaling proteins. The result was that CoTX inhibited IL-33- and IgE-induced activation, phosphorylation of MK2, and transactivation of NF-κB. In a DNCB-induced AD mouse model, CoTX treatment significantly improved AD symptoms and reduced epidermal thickness and mast cell infiltration. Finally, CoTX lowered serum IgE and IL-4 levels.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The study suggests that CoTX has anti-allergic and anti-inflammatory effects in allergic AD. By targeting IL-33 and IgE pathways, CoTX demonstrated potential in regulating mast cell activation and inflammatory cytokine production. The observed improvements in the AD mouse model indicate CoTX as a promising candidate for further research towards developing effective and safe treatments for AD.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"4 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GPD1 relieves the proliferation, migration and invasion abilities of oral cancer cells by inhibiting mitochondrial function","authors":"Qichao Kang, Xiangling Liao, Zhen Du","doi":"10.1007/s13273-024-00445-7","DOIUrl":"https://doi.org/10.1007/s13273-024-00445-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Oral cancer is a very familiar tumor together with a gravely effect on the life of human. GPD1 has been verified to join into the regulation of multifold cancers’ progression through being a suppressor. Interestingly, it has been revealed that GPD1 overexpression activated the PI3K/AKT signaling pathway. However, the regulatory functions of GPD1 on the PI3K/AKT/GSK-3β pathway in oral cancer progression keep vague, and need more investigations.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>To investigate the regulation function and mechanism of GPD1 in oral cancer.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>It was demonstrated that GPD1 exhibited lower expression in oral cancer. Moreover, overexpression of GPD1 relieved cell proliferation and strengthened cell apoptosis in oral cancer. Overexpression of GPD1 weakened cell migration and invasion in oral cancer. In addition, it was confirmed that overexpression of GPD1 suppressed mitochondrial function in oral cancer. At last, it was illustrated that GPD1 triggered the PI3K/AKT/GSK-3β pathway.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>For the first time, this work manifested that GPD1 inhibited the proliferation, migration and invasion of oral cancer cells by inhibiting mitochondrial function through triggering the PI3K/AKT/GSK-3β pathway. This discovery hinted that GPD1 may be a serviceable biomarker for the treatment of oral cancer.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"67 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular targets of histone deacetylase inhibitors in neurodegeneration and neuroprotection","authors":"Yeongwon Park, Shangfei Yu, Seung Yong Hwang, Hyemyung Seo","doi":"10.1007/s13273-024-00441-x","DOIUrl":"https://doi.org/10.1007/s13273-024-00441-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Neurodegenerative diseases show various phenotypes of molecular and cellular malfunction including mitochondrial dysfunction and neuroinflammation. These molecular dynamics are based on the epigenetic regulation of the gene expression in the cells, which are vulnerable to progressive neurodegeneration. Histone deacetylases (HDAC) are the enzymes that remove acetyl group from histones or non-histone proteins for the transcriptional control. Thus, HDAC inhibitors (HDACi) have been proposed as prominent drugs for neurodegenerative diseases.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>In this study, we explain the molecular targets of the HDACi in the processes of neurodegeneration and neuroprotection.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Treatment with HDACi altered the expression of specific genes that are associated with mitochondrial bioenergetics and neuroinflammation.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>Mitochondrial bioenergetics- and neuroinflammation-related molecular targets of HDACi may be the key to the use of HDACi therapy for neurodegenerative diseases.</p><h3 data-test=\"abstract-sub-heading\">Purpose of review</h3><p>We aimed to discover molecular targets of HDACi in progressive neurodegeneration and to use these targets in potential therapeutics to induce neuroprotection.</p><h3 data-test=\"abstract-sub-heading\">Recent findings</h3><p>HDACi reverse cellular pathology in a mechanism involving mitochondrial bioenergetics and neuroinflammation, and the result is alleviation of pathologic phenotypes of neurodegenerative diseases.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"1 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625276","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insight of exercise on dementia; combinatory effects of physical and cognitive exercise","authors":"Hyo-Jeong Cha, Jun Hong Park, Changwan Hong","doi":"10.1007/s13273-024-00440-y","DOIUrl":"https://doi.org/10.1007/s13273-024-00440-y","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Dementia is a progressive neurological disorder which is clinically characterized by memory loss, behavioral symptoms, and loss of ability to live a normal life. Dementia patients may have to cope with permanent and irreversible symptoms.</p><h3 data-test=\"abstract-sub-heading\">Purpose of Review</h3><p>Although a new drug for dementia with beta-amyloid-removal function has recently received FDA approval, the effect of delaying the progression of dementia is still insignificant, but the cost is expensive. On the other hand, studies on the effects of exercise in dementia have implied that the incidence of dementia or cognitive decline could be efficiently controlled by exercise.</p><h3 data-test=\"abstract-sub-heading\">Recent Findings</h3><p>The cognitive neuroprotective effect of exercise was supported by cross-sectional studies in which physically fit seniors showed larger hippocampal or gray matter volumes than unfit seniors. In addition, multiple animal studies demonstrate that exercise promotes neuroplasticity through induction of neurotropic factors, with improved outcomes on cognitive functions.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>In this review, we discuss the effects of conventional mode of physical exercise, cognitive (neuromuscular) exercise, and combined exercise in the prevention of dementia, and highlight the prospects for new exercise programs using digital technology that are being recently developed to reduce cognitive decline. Exercise should be importantly considered as a non-pharmacological therapeutic strategy for cognitive decline and dementia.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"48 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140601396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"MicroRNA-29b-3p reduces cisplatin resistance in non-small cell lung cancer by targeting myeloid cell leukemia-1","authors":"Yuanjun Cheng, Bin Chen, Xuxiao Dong, Jian Shu, Jie Yao","doi":"10.1007/s13273-024-00438-6","DOIUrl":"https://doi.org/10.1007/s13273-024-00438-6","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Introduction</h3><p>Non-small cell lung cancer (NSCLC) is a heterogeneous series of tumors. Given the implication of microRNA-29b-3p (miR-29b-3p) in cisplatin resistance in NSCLC, this study expounded on the further mechanism.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>A549 cells and cisplatin-resistant cells A549/DDP were selected. A549/DDP cells were manipulated with miR-29b-3p mimics/MCL-1 siRNA. miR-29b-3p and MCL levels were assessed. Cell sensitivity to cisplatin of different concentrations was examined by CCK-8. A549/DDP cell apoptosis under 10 µM cisplatin treatment was tested by flow cytometry. The targeted relationship between miR-29b-3p and MCL-1 was analyzed by TargetScan database and dual-luciferase assay. miR-29b-3p and MCL-1 were overexpressed to study whether miR-29b-3p regulated A549/DDP cell drug resistance by targeting MCL-1. To verify the effect of miR-29b-3p on DDP sensitivity in vivo, nude mice were subcutaneously injected with A549/DDP cells carrying the miR-29b-3p overexpressing lentiviral vector or the corresponding control vector to establish the nude mouse xenograft tumor model, and after 3 weeks, injected with DDP via tail vein for 2 weeks.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>miR-29b-3p level in A549/DDP cells was diminished and MCL-1 expression was raised. miR-29b-3p overexpression or MCL-1 silencing enhanced A549/DDP cell sensitivity to cisplatin by promoting apoptosis. miR-29b-3p targeted MCL-1. MCL-1 overexpression partially averted miR-29b-3p overexpression-promoted cisplatin sensitivity and apoptosis. Tumor volume/weight/MCL-1 level in the A549/DDP/miR mimics + DDP group were reduced, and miR-29b-3p was up-regulated versus the A549/DDP/mimics NC + DDP group. Overexpression of miR-29b-3p induced apoptosis in tumor tissues of NSCLC mice.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>miR-29b-3p targeted MCL-1, thus promoting apoptosis and enhancing A549/DDP cell sensitivity to cisplatin.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140601393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Licochalcone B, a natural anti-inflammatory agent, inhibits the inflammatory response and oxidative stress of periodontal ligament cells in periodontitis","authors":"Zhen Du, Xiangling Liao, Qichao Kang","doi":"10.1007/s13273-024-00437-7","DOIUrl":"https://doi.org/10.1007/s13273-024-00437-7","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Periodontitis is a multi-microbial infection characterized by a destructive inflammatory process that affects periodontal tissues. The extracts of traditional Chinese medicine have been reported to be involved in the regulation of the treatment of periodontitis. Licochalcone B (LicB) has been shown to have a wide range of pharmacological activities in diversiform diseases. However, the regulatory functions of LicB and its related mechanisms have not been explored in periodontitis.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>In this study, our work focused on investigating the regulatory functions of LicB in LPS-stimulated PDLCs.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Periodontal ligament cells (PDLCs) were first treated with LPS (10 μg/mL) to simulate periodontitis cell model. The results showed that cell proliferation was decreased after LPS treatment, but this effect was restored after LicB treatment. In addition, LicB inhibited inflammatory response and oxidative stress in LPS-induced PDLCs. Furthermore, the osteogenic differentiation was inhibited after LPS treatment, but this change was reversed by LicB treatment. Lastly, it was demonstrated that LicB blocked the NF-κB/NLRP3 signaling pathway.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>This study for the first time demonstrated that LicB inhibited the inflammatory response and oxidative stress of PDLCs in periodontitis, suggesting that LicB may be a useful drug for periodontitis treatment.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"30 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140601395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tolylfluanid induces developmental toxicity via liver dysfunction in zebrafish embryos","authors":"Taeyeon Hong, Hahyun Park, Gwonhwa Song, Whasun Lim","doi":"10.1007/s13273-024-00436-8","DOIUrl":"https://doi.org/10.1007/s13273-024-00436-8","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Tolylfluanid is a phenylsulfamide fungicide used to mitigate enormous losses in agriculture and coastal industries. Previous studies have reported that exposure to tolylfluanid causes metabolic dysfunction, such as fat accumulation. Additionally, exposure to tolylfluanid used to be detected in strawberries at levels exceeding the maximum residue limit. However, no studies on early developmental toxicity in zebrafish models have been reported.</p><h3 data-test=\"abstract-sub-heading\">Objectives</h3><p>This study aimed to investigate the toxic effects of tolylfluanid on the early stages of zebrafish development.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>At low tolylfluanid concentrations, survival rates, hatching rates, and yolk sac morphology remained unchanged. However, body length and eye size were slightly reduced compared to those of the control. In particular, <i>olig2</i> transgenic zebrafish exposed to tolylfluanid exhibited impaired motor neuron formation, leading to reduced motor neuron length. Furthermore, tolylfluanid decreased liver size in <i>fabp10a</i> transgenic zebrafish larvae, inducing liver-specific red fluorescence. However, tolylfluanid exposure did not affect the vasculature of zebrafish embryos in the <i>fli1a</i>:eGFP transgenic model.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Tolylfluanid disrupts organogenesis, particularly in motor neurons and the liver, during early development in zebrafish. Additionally, the results provide reference points for the concentration conditions that can be used in aquatic ecosystems.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"31 9 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140602232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cheong-sang-gyeon-tong-tang improves hepatic steatosis by regulating cholesterol metabolism","authors":"Yun-Mi Kang, Kwang-Youn Kim, Tae In Kim, Yeon-Ji Kim, Han-Hae Kim, Kyungho Kim","doi":"10.1007/s13273-024-00426-w","DOIUrl":"https://doi.org/10.1007/s13273-024-00426-w","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Hepatic steatosis is characterized by lipid accumulation in hepatocytes. Cheong-sang-gyeon-tong-tang is a major prescription for all types of headaches in traditional East Asian medicine.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study aimed to investigate the pharmacological effects of Cheong-sang-gyeon-tong-tang extract (CG) on high-fat diet (HFD)-induced hepatic steatosis in mice and to explore the underlying mechanism.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Treatment with CG significantly reduced body weight, liver weight, and epididymal fat mass, as well as improved the serum and hepatic lipid profiles in the HFD-induced fatty liver mouse model. Further, CG alleviated lipid accumulation in HFD-fed mice by controlling lipid metabolism, including triglyceride and cholesterol synthesis, and fatty acid oxidation at the mRNA level. CG also regulated the expression of cholesterol regulatory proteins in HFD-induced fatty liver mice.</p><h3 data-test=\"abstract-sub-heading\">Conclusions</h3><p>These results indicate that CG alleviates hepatic steatosis by regulating cholesterol homeostasis in HFD-induced fatty liver mice, thus improving our understanding of the mechanisms by which CG improves hepatic steatosis. Therefore, we propose CG as a therapeutic candidate for lipid metabolic disorders such as fatty liver disease.</p>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"10 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140076228","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of glioblastoma invasion triggered by system Xc−-mediated glutamate release","authors":"","doi":"10.1007/s13273-024-00433-x","DOIUrl":"https://doi.org/10.1007/s13273-024-00433-x","url":null,"abstract":"<h3>Abstract</h3> <span> <h3>Backgrounds</h3> <p>Glioblastoma (GBM) is a highly aggressive brain cancer associated with poor prognosis, primarily attributed to its profound invasive characteristics. Glutamate is the main cause of invasion, and invasion is promoted by system Xc⁻ (cystine/glutamate antiporter), which is highly expressed in GBM. To date, no studies have examined the relationship between invasion and the specific downregulation of system Xc⁻ (xCT or <em>SLC7A11</em>) using shRNA in GBM.</p> </span> <span> <h3>Objective</h3> <p>We aimed to determine the effect of a specific knockdown system, Xc⁻, in GBM using short hairpin RNA (shRNA) rather than pharmacological approaches.</p> </span> <span> <h3>Results</h3> <p>Invasion was inhibited in GBM cells treated with sulfasalazine, a system Xc⁻ inhibitor. Our experiments validated a reduction in extracellular glutamate concentration following sulfasalazine treatment, without affecting GBM proliferation or calcium response. However, the efficacy of pharmacological methods is hindered by nonspecific effects and the prevalence of multiple side effects. Therefore, we specifically targeted the system Xc⁻ molecule through shRNA. Downregulation using shRNA demonstrated decreased invasion and extracellular glutamate levels, without affecting the calcium response and proliferation.</p> </span> <span> <h3>Conclusion</h3> <p>The targeted inhibition of system Xc⁻ using shRNA yields a notable reduction in GBM invasion.</p> </span>","PeriodicalId":18683,"journal":{"name":"Molecular & Cellular Toxicology","volume":"36 1","pages":""},"PeriodicalIF":1.7,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140071585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}