Toxicology in Vitro最新文献

The impact of bisphenol AF on skeletal muscle function and differentiation in vitro. 双酚 AF 对体外骨骼肌功能和分化的影响

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-23 DOI: 10.1016/j.tiv.2024.105975

Minying Cui, Foteini Tzioufa, Joseph Bruton, Håkan Westerblad, Vesna Munic Kos

{"title":"The impact of bisphenol AF on skeletal muscle function and differentiation in vitro.","authors":"Minying Cui, Foteini Tzioufa, Joseph Bruton, Håkan Westerblad, Vesna Munic Kos","doi":"10.1016/j.tiv.2024.105975","DOIUrl":"https://doi.org/10.1016/j.tiv.2024.105975","url":null,"abstract":"<p><p>Various environmental chemicals have been identified as contributors to metabolic diseases. Bisphenol AF (BPAF), a substitute for bisphenol A, has been associated with changes in glucose metabolism and incidence of type 2 diabetes mellitus in humans. However, its mode of action remains unclear. Considering that skeletal muscle is the primary tissue for glucose utilization and the development of insulin resistance, yet largely neglected in toxicological assessments, we investigated the impact of BPAF on skeletal muscle function and differentiation. We examined the effects of BPAF (0.01-10 μM) on glucose uptake, response to insulin, production of reactive oxygen species (ROS), intracellular calcium, and myocyte differentiation, during hyperglycemia, insulin stimulation, and muscle contraction. We used the rat myoblast cell line L6 differentiated into myotubes, and murine primary isolated muscle fibers. In myotubes and contracting adult fibers, BPAF increased mitochondrial ROS. Basal glucose uptake was increased in myotubes while cells' ability to respond to insulin was decreased. Additionally, in developing myotubes, differentiation markers were downregulated with BPAF, along with impaired formation of tube structures. These effects were primarily observed at 10 μM concentration, which is markedly higher than reported human exposure concentrations. The results provide an insight into potential hazards associated with BPAF in terms of metabolic disruption in skeletal muscle. The developed in vitro methods show promise for future usage in assessments of new chemicals and their mixtures.</p>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":" ","pages":"105975"},"PeriodicalIF":2.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Polyamine-modified naphthalimide derivative 9C inhibits colorectal cancer through ROS-mediated ER stress, migration and invasion. 多胺修饰的萘二甲酰亚胺衍生物 9C 通过 ROS 介导的 ER 应激、迁移和侵袭抑制结直肠癌。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-23 DOI: 10.1016/j.tiv.2024.105974

Xiaojuan Xu, Chaochao Ge, Senzhen Wang, Lei Gao, Chaojie Wang, Fujun Dai, Yuxia Wang, Songqiang Xie

{"title":"Polyamine-modified naphthalimide derivative 9C inhibits colorectal cancer through ROS-mediated ER stress, migration and invasion.","authors":"Xiaojuan Xu, Chaochao Ge, Senzhen Wang, Lei Gao, Chaojie Wang, Fujun Dai, Yuxia Wang, Songqiang Xie","doi":"10.1016/j.tiv.2024.105974","DOIUrl":"https://doi.org/10.1016/j.tiv.2024.105974","url":null,"abstract":"<p><p>Mounting evidence over the past decades has demonstrated the therapeutic potential of targeting endoplasmic reticulum (ER) stress signaling in cancer. Naphthalimdes exert their anti-cancer activities in a variety of ways. However, the effects of naphthalimides on ER stress are rarely reported. In this study, based on RNA-sequencing analysis, we observed that 9C, a naphthalimide derivative, could trigger ER stress to activate death receptor signaling and autophagy. Pretreatment of ER stress inhibitor, such as salubrinal, and autophagy inhibitor, such as 3-methyladenine (3-MA), partially reversed 9C-induced inhibition of cell growth. Furthermore, our results unveiled a reactive oxygen species (ROS)-dependent inhibitory effect of 9C. In addition, 9C inhibited colorectal cancer (CRC) cells migration and invasion. Removal of ROS using N-acetyl-L-cysteine (NAC) attenuated the expression of ATF4, CHOP, death receptors, E-cadherin, and the apoptosis and autophagy related proteins. Taken together, our results suggested that ROS-mediated ER stress, migration, and invasion is responsible for the therapeutic potential of naphthalimides including 9C in CRC.</p>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":" ","pages":"105974"},"PeriodicalIF":2.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142717830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of Beauvericin metabolites using rat and human liver microsomes and in vivo urinary excretion study in rats for biomonitoring application 利用大鼠和人类肝脏微粒体鉴定蒲公英代谢物，并对大鼠进行体内尿排泄研究，以用于生物监测。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-20 DOI: 10.1016/j.tiv.2024.105969

Anushka Pandey , C. Yahavi , Manisha Bhateria , Abdul Rahman Khan , Sheelendra Pratap Singh

{"title":"Identification of Beauvericin metabolites using rat and human liver microsomes and in vivo urinary excretion study in rats for biomonitoring application","authors":"Anushka Pandey , C. Yahavi , Manisha Bhateria , Abdul Rahman Khan , Sheelendra Pratap Singh","doi":"10.1016/j.tiv.2024.105969","DOIUrl":"10.1016/j.tiv.2024.105969","url":null,"abstract":"<div><div>Beauvericin (BEA), an emerging mycotoxin, belongs to a class characterized by a cyclic depsipeptide ring structure, commonly produced by fungal species like <em>Fusarium sp.</em> and <em>Beauveria bassiana</em>. BEA is known for contaminating cereals and grains (wheat, maize). Humans might be exposed to BEA through contaminated food. Biomonitoring is a valuable method for assessing environmental and occupational exposure to specific chemicals. These studies measure chemical biomarkers to quantify exposure for public health risk assessment. However, identifying specific and sensitive chemical biomarkers for BEA exposure remains challenging. In the present study, metabolites of BEA were identified through <em>in vitro</em> metabolism studies conducted in the rat (RLM) and human liver microsomes (HLM) using the liquid chromatography-high resolution mass spectrometry (LC-HRMS) technique. Seventeen metabolites were characterized, showcasing products of oxidation, reduction, and deamination reactions. Predominantly, oxidative metabolites resulting from mono‑oxygenation, di‑oxygenation, and tri‑oxygenation were observed. The metabolites in RLM primarily consisted of mono and di‑oxygenated forms, while in HLM, tri‑oxygenated and demethylated products were also found. Furthermore, <em>in vivo</em> excretion study in rat urine samples confirmed the presence of oxygenated metabolites detected in the <em>in vitro</em> samples. Consequently, the study suggests that oxygenated metabolites of BEA could serve as useful biomarkers for conducting future biomonitoring studies.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105969"},"PeriodicalIF":2.6,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142689669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tripartite motif 22 interacts with protein phosphatase magnesium-dependent 1 A to aggravate radiation-induced epithelial-mesenchymal transition and fibrogenesis in lung epithelial cells 三方基序 22 与蛋白磷酸酶镁依赖性 1 A 相互作用，加剧辐射诱导的肺上皮细胞上皮-间充质转化和纤维化。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-17 DOI: 10.1016/j.tiv.2024.105972

Jinhua Lu , Menglei Wang , Yeyue Zhou , Yazhen Zhong , Shengyou Lin

{"title":"Tripartite motif 22 interacts with protein phosphatase magnesium-dependent 1 A to aggravate radiation-induced epithelial-mesenchymal transition and fibrogenesis in lung epithelial cells","authors":"Jinhua Lu , Menglei Wang , Yeyue Zhou , Yazhen Zhong , Shengyou Lin","doi":"10.1016/j.tiv.2024.105972","DOIUrl":"10.1016/j.tiv.2024.105972","url":null,"abstract":"<div><div>Radiation-induced lung injury (RILI) is the damage to lung tissue caused by radiation. Epithelial-mesenchymal transition (EMT) and fibrogenesis in radiated lung epithelial cells play critical roles in RILI. Tripartite motif-containing (TRIM) family proteins have been shown to be involved in fibrotic diseases, but whether TRIM22 plays a role in RILI and relative underlying mechanism remain unexplored. Here, we reported a unique comprehensive analysis of the impact of TRIM22 on radiation-induced EMT and fibrogenesis in A549 and BEAS-2B cells. Cell viability and proliferation were measured by Cell-Counting Kit (CCK)-8 and colony formation assays. The interaction between TRIM22 and protein phosphatase magnesium-dependent 1 A (PPM1A) was validated using co-immunoprecipitation. A chromatin immunoprecipitation assay was used to verify the interaction between SMAD3 and TRIM22 promoter. Cell viability and proliferation were decreased by 8 Gy raddition. TRIM22 was elevated in a dose- and time-dependent manner after radiation, and its knockdown reduced EMT and fibrogenesis. TRIM22 could interact with PPM1A and promote its ubiquitination to activate the TGF-β1/Smad pathway. The overexpression of PPM1A abolished TRIM22-mediated EMT and fibrogenesis. Meanwhile, SMAD3 could bind to the TRIM22 promoter to elevate its expression. This study revealed a novel TRIM22/PPM1A/Smad3 signaling pathway that contributes to the raddition-induced EMT and fibrogenesis, which would provide novel targets and strategies for treating RILI.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105972"},"PeriodicalIF":2.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142669776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Conditioned medium of human umbilical cord-mesenchymal stem cells cultivated with human cord blood serum enhances stem cell stemness and secretome profiles 用人脐带血血清培养人脐带间充质干细胞的条件培养基可增强干细胞的干性和分泌组特征。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-17 DOI: 10.1016/j.tiv.2024.105973

Palakorn Kaokaen, Amorn Pangjantuk, Phongsakorn Kunhorm, Wilasinee Promjantuek, Nipha Chaicharoenaudomrung, Parinya Noisa

{"title":"Conditioned medium of human umbilical cord-mesenchymal stem cells cultivated with human cord blood serum enhances stem cell stemness and secretome profiles","authors":"Palakorn Kaokaen, Amorn Pangjantuk, Phongsakorn Kunhorm, Wilasinee Promjantuek, Nipha Chaicharoenaudomrung, Parinya Noisa","doi":"10.1016/j.tiv.2024.105973","DOIUrl":"10.1016/j.tiv.2024.105973","url":null,"abstract":"<div><div>The proteins secreted by human umbilical cord mesenchymal stem cells (hUC-MSCs) may enhance tissue regeneration and wound healing. Traditional hUC-MSC cultures may not be enough since they undergo recurrent cellular senescence during large-scale production. This decreases the therapeutic ability of hUC-MSCs by altering genes and proteins that control stemness, proliferation, and protein release. Human cord blood serum (CBS) and the middle-density technique were used to evaluate hUC-MSC regeneration ability. To evaluate early-passage hMSCs for secretome-based therapies, they were expanded and secreted in vitro. After 4 days, hUC-MSCs cultivated at 3000 cells/cm<sup>2</sup> and supplemented with 1 ng/ml CBS showed increased growth, cell proliferation, and a much lower population doubling time. CBS treatment reduced CD34, CD45, and HLA-DR levels in human umbilical cord mesenchymal stem cells (hUC-MSCs) by less than 2 %. Positive markers such CD73, CD90, and CD105 were found at >97 %, like control hUC-MSCs. Over extended culture, this combination culture can increase survival, proliferation, and stemness and postpone cell death and hUC-MSC senescence. The protein profile and hUC-MSC secretion were improved to make MSC secretion protein therapeutic. This improves cell-free treatment, proliferation, and wound healing in human skin cells. To improve cell-based transplantation or cosmeceutical manufacturing, this technique can boost hUC-MSC regeneration capacity.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105973"},"PeriodicalIF":2.6,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Tannic acid modulates SARS-CoV-2 pathogenesis by curbing key host receptors and oxidative stress 单宁酸通过抑制关键宿主受体和氧化应激调节 SARS-CoV-2 的发病机制

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-16 DOI: 10.1016/j.tiv.2024.105971

Akshaya Rani Augustus , Yashwanth Radhakrishnan , James Prabhanand Bhaskar , Suresh Ramamurthi , Karutha Pandian Shunmugiah

{"title":"Tannic acid modulates SARS-CoV-2 pathogenesis by curbing key host receptors and oxidative stress","authors":"Akshaya Rani Augustus , Yashwanth Radhakrishnan , James Prabhanand Bhaskar , Suresh Ramamurthi , Karutha Pandian Shunmugiah","doi":"10.1016/j.tiv.2024.105971","DOIUrl":"10.1016/j.tiv.2024.105971","url":null,"abstract":"<div><div>The novel coronavirus SARS-CoV-2, which wrecked havoc around the world in the recent years through COVID-19, gains entry into the host cell through various receptors. Development of therapies targeting host–pathogen interaction will be a key to curb the infection as it potentially suppresses viral attachment and entry into the host. Boundless bioactives abundant in natural resources are the important source of new as well as safer alternatives. Tannic acid, a polyphenolic compound found abundantly in various plant sources, has gained much attention owing to its multifaceted pharmacological properties. This research paper presents a comprehensive investigation on antioxidant, anti-inflammatory and anti-viral abilities of tannic acid, substantiated through a triad of methodologies: <em>in silico</em>, <em>in vitro</em> and <em>in vivo</em> approaches. <em>In vitro</em> experiments, confirmed the antioxidant and anti-inflammatory efficacy as well as the host receptor modulating potential of tannic acid. <em>In silico</em> docking analyses elucidated the molecular interactions between tannic acid and key host receptors involved in inflammation and viral pathogenesis. Furthermore, the <em>in vivo</em> studies involving <em>Danio rerio</em> provided a holistic understanding of the systemic impact of tannic acid, including its antioxidant effects by mitigating the oxidative stress.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105971"},"PeriodicalIF":2.6,"publicationDate":"2024-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142649732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cyclosporin A toxicity on endothelial cells differentiated from induced pluripotent stem cells: Assembling an adverse outcome pathway. 环孢素 A 对诱导多能干细胞分化的内皮细胞的毒性：构建不良后果途径

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-14 DOI: 10.1016/j.tiv.2024.105954

Zahra Mazidi, Matthias Wieser, Nicoleta Spinu, Adelheid Weidinger, Andrey V Kozlov, Kristijan Vukovic, Sara Wellens, Cormac Murphy, Pranika Singh, Liadys Mora Lagares, Madhusudhan Reddy Bobbili, Lisa Liendl, Markus Schosserer, Andreas Diendorfer, Dieter Bettelheim, Wolf Eilenberg, Thomas Exner, Maxime Culot, Paul Jennings, Anja Wilmes, Marjana Novic, Emilio Benfenati, Regina Grillari-Voglauer, Johannes Grillari

{"title":"Cyclosporin A toxicity on endothelial cells differentiated from induced pluripotent stem cells: Assembling an adverse outcome pathway.","authors":"Zahra Mazidi, Matthias Wieser, Nicoleta Spinu, Adelheid Weidinger, Andrey V Kozlov, Kristijan Vukovic, Sara Wellens, Cormac Murphy, Pranika Singh, Liadys Mora Lagares, Madhusudhan Reddy Bobbili, Lisa Liendl, Markus Schosserer, Andreas Diendorfer, Dieter Bettelheim, Wolf Eilenberg, Thomas Exner, Maxime Culot, Paul Jennings, Anja Wilmes, Marjana Novic, Emilio Benfenati, Regina Grillari-Voglauer, Johannes Grillari","doi":"10.1016/j.tiv.2024.105954","DOIUrl":"https://doi.org/10.1016/j.tiv.2024.105954","url":null,"abstract":"<p><p>Cyclosporin A (CSA) is a potent immunosuppressive agent in pharmacologic studies. However, there is evidence for side effects, specifically in regard to vascular dysfunction. Its mode of action inducing endothelial cell toxicity is partially unclear, and a connection with an adverse outcome pathway (AOP) is not established yet. Therefore, we designed this study to get deeper insights into the mechanistic toxicology of CSA on angiogenesis. Stem cells, especially induced pluripotent stem cells (iPSCs) with the ability of differentiation to all organs of the body, are considered a promising in vitro model to reduce animal experimentation. In this study, we differentiated iPSCs to endothelial cells (ECs) as one cell type that in other studies would allow to generate cells or organoids from single donors. Flow cytometry and immunostaining confirmed our scalable differentiation protocol. Then dose and time course experiments assessing CSA cytotoxicity on iPS derived endothelial cells were performed. Transcriptomic data suggested CDA dependent induction of reactive oxygen species (ROS) and mitochondrial dysfunction, which was confirmed by in vitro experiments. Additionally, CSA impaired angiogenesis via ROS induction. Finally, we combined this information into an AOP, was developed based on here observed and literature based evidence for CSA-mediated endothelial cell toxicity. This AOP will help to design in vitro test batteries, model events observed in human toxicity studies, as well for predictive toxicology.</p>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":" ","pages":"105954"},"PeriodicalIF":2.6,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645209","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In vitro toxicity of two functionalized reduced graphene oxide materials with potential application in food packaging 具有食品包装应用潜力的两种功能化还原氧化石墨烯材料的体外毒性。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-13 DOI: 10.1016/j.tiv.2024.105970

Óscar Cebadero-Domínguez , Leticia Diez-Quijada , Sergio López , Alejandro Prieto , María Puerto , Ana M. Cameán , Angeles Jos

{"title":"In vitro toxicity of two functionalized reduced graphene oxide materials with potential application in food packaging","authors":"Óscar Cebadero-Domínguez , Leticia Diez-Quijada , Sergio López , Alejandro Prieto , María Puerto , Ana M. Cameán , Angeles Jos","doi":"10.1016/j.tiv.2024.105970","DOIUrl":"10.1016/j.tiv.2024.105970","url":null,"abstract":"<div><div>Functionalized graphene materials have been proposed as nanofillers in food packaging applications as they improve the characteristics of the resulting nanocomposites. But food contact materials require a toxicity evaluation previous their authorization and use. In this sense, reduced graphene oxide functionalized with dodecyl amine (DA-rGO), and [2-(methacryloyloxy) ethyl] trimethylammonium chloride (MTAC-rGO) were characterized and their internalization and cytotoxicity in Caco-2 and HepG2 cultures evaluated. Cell viability decreased from 100 μg/mL in all experimental trials, and oxidative stress by means of a reduction in glutathione levels was evidenced as one of the potential toxicity mechanisms involved. Moreover, both materials were subjected to an <em>in vitro</em> digestion process to investigate their potential changes along the gastrointestinal tract. Digested samples were characterized, and the cytotoxicity also evaluated showing an exacerbation. These results raise concerns about the impact of these materials after oral exposure, and therefore further research is necessary.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105970"},"PeriodicalIF":2.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632338","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Corrigendum to “Exploring the combined impact of cisplatin and copper-cysteamine nanoparticles through Chemoradiation: An in-vitro study” [Toxicology in vitro 99 (2024) 105878]. 对 "探索顺铂和半胱氨酸铜纳米粒子通过化学放疗产生的综合影响：一项体外研究 "的更正 [Toxicology in vitro 99 (2024 105878]：体外研究" [Toxicology in vitro 99 (2024) 105878]。

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-12 DOI: 10.1016/j.tiv.2024.105968

Mahsa Ejtema , Nahid Chegeni , Amanollah Zarei-Ahmady , Zeinab Salehnia , Masoumeh Shamsi , Sasan Razmjoo

引用次数: 0

Anticancer activity of EMD37 against human head and neck cancer: Impact on apoptotic and inflammatory machineries EMD37 对人类头颈癌的抗癌活性：对凋亡和炎症机制的影响

IF 2.6 3区医学

Toxicology in Vitro Pub Date : 2024-11-05 DOI: 10.1016/j.tiv.2024.105967

Marwa Sharaky , Eman M.E. Dokla , Amal Kamal Abdel-Aziz

{"title":"Anticancer activity of EMD37 against human head and neck cancer: Impact on apoptotic and inflammatory machineries","authors":"Marwa Sharaky , Eman M.E. Dokla , Amal Kamal Abdel-Aziz","doi":"10.1016/j.tiv.2024.105967","DOIUrl":"10.1016/j.tiv.2024.105967","url":null,"abstract":"<div><div>Accumulating evidence emphasizes the tumorigenic role of epidermal growth factor receptor (EGFR) in head and neck cancer (HNC). Although cetuximab is the sole anti-EGFR approved by the Food and Drug Administration for treating HNC patients.its response rates are modest. Thus, novel effective and tolerable therapeutic strategies are urged. We previously reported the capability of oxadiazole derivatives to degrade tyrosine kinase receptors including EGFR and exhibit potent anticancer activities against NCI-60 panel which does not include HNC. The aim of this study was to investigate the potential anticancer activity of EMD37, a novel 1,2,4-oxadiazole derivative, against human HNC cells and if effective, to examine the effect of EMD37 on apoptotic and inflammation mediators. Indeed, EMD37 exhibited potent cytotoxicity against patient-derived HNC cell lines (HNO-97, HN-9 and FaDu). Delving deeper, EMD37 triggered intrinsic and extrinsic apoptosis in HNC cells as evidenced by increased levels of caspase-8, caspase-9, caspase-3, caspase-7, caspase-6, TP53BP1 tumor suppressor and Bax, and downregulated anti-apoptotic Bcl-2 protein. EMD37 also significantly abrogated the levels of pro-inflammatory interleukin-1β, interleukin-6, cyclooxygenase-2 and matrix metalloproteinases (MMP-2 and MMP-9) which are heightened in HNC. Bioinformatic analysis revealed that BCL2<sup>low</sup>, IL6<sup>low</sup> and MMP9<sup>low</sup> HNC biospecimens are enriched with epithelial cell differentiation gene set, and CASP8<sup>high</sup> cohort is enriched with extrinsic apoptosis. Altogether, this study emphasizes the therapeutic potential of targeting the apoptotic and inflammatory machineries in HNC using EMD37.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105967"},"PeriodicalIF":2.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0