Pub Date : 2024-11-16DOI: 10.1016/j.tiv.2024.105971
Akshaya Rani Augustus , Yashwanth Radhakrishnan , James Prabhanand Bhaskar , Suresh Ramamurthi , Karutha Pandian Shunmugiah
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: in silico, in vitro and in vivo approaches. In vitro experiments, confirmed the antioxidant and anti-inflammatory efficacy as well as the host receptor modulating potential of tannic acid. In silico docking analyses elucidated the molecular interactions between tannic acid and key host receptors involved in inflammation and viral pathogenesis. Furthermore, the in vivo studies involving Danio rerio provided a holistic understanding of the systemic impact of tannic acid, including its antioxidant effects by mitigating the oxidative stress.
{"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}
Pub Date : 2024-11-15DOI: 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 , Bruno Bettelheim , Wolf Eilenberg , Thomas Exner , Maxime Culot , Paul Jennings , Anja Wilmes , Johannes Grillari
Cyclosporin A (CSA) is a potent immunosuppressive agent in pharmacologic studies. However, there is evidence for side effects, specifically regarding 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 multi-cell type 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 CSA dependent induction of reactive oxygen species (ROS), mitochondrial dysfunction, and impaired angiogenesis via ROS induction which was confirmed by in vitro experiments. In order to put these data into a potential adverse outcome pathway (AOP) context, we performed a literature review for CSA-mediated endothelial cell toxicity and combined our experimental data with the publicly available knowledge. Such an AOP will help to design in vitro test batteries and to model events observed in human toxicity studies, as well in predictive toxicology.
{"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 , Bruno Bettelheim , Wolf Eilenberg , Thomas Exner , Maxime Culot , Paul Jennings , Anja Wilmes , Johannes Grillari","doi":"10.1016/j.tiv.2024.105954","DOIUrl":"10.1016/j.tiv.2024.105954","url":null,"abstract":"<div><div>Cyclosporin A (CSA) is a potent immunosuppressive agent in pharmacologic studies. However, there is evidence for side effects, specifically regarding 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 <em>in vitro</em> 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 multi-cell type 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 CSA dependent induction of reactive oxygen species (ROS), mitochondrial dysfunction, and impaired angiogenesis <em>via</em> ROS induction which was confirmed by <em>in vitro</em> experiments. In order to put these data into a potential adverse outcome pathway (AOP) context, we performed a literature review for CSA-mediated endothelial cell toxicity and combined our experimental data with the publicly available knowledge. Such an AOP will help to design <em>in vitro</em> test batteries and to model events observed in human toxicity studies, as well in predictive toxicology.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"103 ","pages":"Article 105954"},"PeriodicalIF":2.6,"publicationDate":"2024-11-15","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}
Pub Date : 2024-11-13DOI: 10.1016/j.tiv.2024.105970
Óscar Cebadero-Domínguez , Leticia Diez-Quijada , Sergio López , Alejandro Prieto , María Puerto , Ana M. Cameán , Angeles Jos
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 in vitro 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.
{"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}
{"title":"Corrigendum to “Exploring the combined impact of cisplatin and copper-cysteamine nanoparticles through Chemoradiation: An in-vitro study” [Toxicology in vitro 99 (2024) 105878].","authors":"Mahsa Ejtema , Nahid Chegeni , Amanollah Zarei-Ahmady , Zeinab Salehnia , Masoumeh Shamsi , Sasan Razmjoo","doi":"10.1016/j.tiv.2024.105968","DOIUrl":"10.1016/j.tiv.2024.105968","url":null,"abstract":"","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105968"},"PeriodicalIF":2.6,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142632274","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}
Pub Date : 2024-11-05DOI: 10.1016/j.tiv.2024.105967
Marwa Sharaky , Eman M.E. Dokla , Amal Kamal Abdel-Aziz
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 BCL2low, IL6low and MMP9low HNC biospecimens are enriched with epithelial cell differentiation gene set, and CASP8high cohort is enriched with extrinsic apoptosis. Altogether, this study emphasizes the therapeutic potential of targeting the apoptotic and inflammatory machineries in HNC using EMD37.
{"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}
Pub Date : 2024-10-30DOI: 10.1016/j.tiv.2024.105959
Alok Kumar Pandey, Vishal Trivedi
Accumulation of hemin in cells, tissues, and organs is one of the major pathological conditions linked to hemolytic diseases like malaria. Pro-oxidant hemin confers high toxicity following its accumulation. We tested the cellular toxicity of hemin on HepG2 cells by exploring modulation in various cellular characteristics. Hemin reduces the viability of HepG2 cells and brings about visible morphological changes. Hemin causes perforations on the surface of HepG2 cells observed through SEM. Hemin leads to the extracellular release of liver enzymes and reduces the wound-healing potential of HepG2 cells. Hemin leads to the fragmentation of HepG2 DNA, arrests the cell cycle progression in the S-phase and induces apoptosis in these cells. Western blot analysis revealed that hemin triggers both the extrinsic and intrinsic pathways of apoptosis in HepG2 cells. We have already shown that the cytoprotective protein HSPA8 can polymerize hemin and minimize its toxicity. Similar experiments with hemin in the presence and absence of HSPA8 showed that HSPA8 reverses all the tested toxic effects of hemin on HepG2 cells. The protection from hemin toxicity in HepG2 cells appeared to be due to the extracellular polymerization of hemin by HSPA8.
{"title":"Heat shock protein HSPA8 impedes hemin-induced cellular-toxicity in liver","authors":"Alok Kumar Pandey, Vishal Trivedi","doi":"10.1016/j.tiv.2024.105959","DOIUrl":"10.1016/j.tiv.2024.105959","url":null,"abstract":"<div><div>Accumulation of hemin in cells, tissues, and organs is one of the major pathological conditions linked to hemolytic diseases like malaria. Pro-oxidant hemin confers high toxicity following its accumulation. We tested the cellular toxicity of hemin on HepG2 cells by exploring modulation in various cellular characteristics. Hemin reduces the viability of HepG2 cells and brings about visible morphological changes. Hemin causes perforations on the surface of HepG2 cells observed through SEM. Hemin leads to the extracellular release of liver enzymes and reduces the wound-healing potential of HepG2 cells. Hemin leads to the fragmentation of HepG2 DNA, arrests the cell cycle progression in the S-phase and induces apoptosis in these cells. Western blot analysis revealed that hemin triggers both the extrinsic and intrinsic pathways of apoptosis in HepG2 cells. We have already shown that the cytoprotective protein HSPA8 can polymerize hemin and minimize its toxicity. Similar experiments with hemin in the presence and absence of HSPA8 showed that HSPA8 reverses all the tested toxic effects of hemin on HepG2 cells. The protection from hemin toxicity in HepG2 cells appeared to be due to the extracellular polymerization of hemin by HSPA8.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105959"},"PeriodicalIF":2.6,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565316","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}
Pub Date : 2024-10-24DOI: 10.1016/j.tiv.2024.105957
Alina Uribe-García , Estefany I. Medina-Reyes , Carlos A. Flores-Reyes , Alejandro A. Zagal-Salinas , Octavio Ispanixtlahuatl-Meraz , Eduardo Delgado-Armenta , Miguel Santibáñez-Andrade , Cesar M. Flores , Yesennia Sánchez-Pérez , Claudia M. García-Cuéllar , Yolanda I. Chirino
Background
Food-grade titanium dioxide (E171) has been under scrutiny in the last decade since its possible adverse effects; however, the cellular mechanisms underlying E171 toxicity have not been thoroughly described.
Aim
We aimed to compare the effects of E171 on endoplasmic reticulum (ER) homeostasis in normal and cancer colon cells.
Experimental design
We exposed normal, carcinoma, and adenocarcinoma cells to 0.1, 1, 10, 50 and 100 μg/cm2 of E171 for 24, 48 and 72 h, and we evaluated ER stress, cell viability, titanium uptake, intracellular calcium concentration, and gene expression related to unfolded protein response (UPR) and chaperone pathways.
Results
Cell viability decreased only after 72 h of exposure to 100 μg/cm2 of E171. Adenocarcinoma cells internalized higher titanium amounts than normal and carcinoma cells, but the effects in ER distribution, intracellular calcium concentration, and gene expression were similar among the three cell lines. The expression of UPR and chaperone pathways were downregulated at the lowest concentrations but upregulated at the highest concentrations in the three cell lines.
Conclusion
E171 induces ER stress through alterations in ER distribution, intracellular calcium, and UPR and chaperone protein pathways.
{"title":"Food grade titanium dioxide induced endoplasmic reticulum stress in colon cells: Comparison between normal and colorectal carcinoma cells","authors":"Alina Uribe-García , Estefany I. Medina-Reyes , Carlos A. Flores-Reyes , Alejandro A. Zagal-Salinas , Octavio Ispanixtlahuatl-Meraz , Eduardo Delgado-Armenta , Miguel Santibáñez-Andrade , Cesar M. Flores , Yesennia Sánchez-Pérez , Claudia M. García-Cuéllar , Yolanda I. Chirino","doi":"10.1016/j.tiv.2024.105957","DOIUrl":"10.1016/j.tiv.2024.105957","url":null,"abstract":"<div><h3>Background</h3><div>Food-grade titanium dioxide (E171) has been under scrutiny in the last decade since its possible adverse effects; however, the cellular mechanisms underlying E171 toxicity have not been thoroughly described.</div></div><div><h3>Aim</h3><div>We aimed to compare the effects of E171 on endoplasmic reticulum (ER) homeostasis in normal and cancer colon cells.</div></div><div><h3>Experimental design</h3><div>We exposed normal, carcinoma, and adenocarcinoma cells to 0.1, 1, 10, 50 and 100 μg/cm<sup>2</sup> of E171 for 24, 48 and 72 h, and we evaluated ER stress, cell viability, titanium uptake, intracellular calcium concentration, and gene expression related to unfolded protein response (UPR) and chaperone pathways.</div></div><div><h3>Results</h3><div>Cell viability decreased only after 72 h of exposure to 100 μg/cm<sup>2</sup> of E171. Adenocarcinoma cells internalized higher titanium amounts than normal and carcinoma cells, but the effects in ER distribution, intracellular calcium concentration, and gene expression were similar among the three cell lines. The expression of UPR and chaperone pathways were downregulated at the lowest concentrations but upregulated at the highest concentrations in the three cell lines.</div></div><div><h3>Conclusion</h3><div>E171 induces ER stress through alterations in ER distribution, intracellular calcium, and UPR and chaperone protein pathways.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105957"},"PeriodicalIF":2.6,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513029","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}
Pub Date : 2024-10-21DOI: 10.1016/j.tiv.2024.105958
Zuleyha Demirci , Zeynep Islek , Halime Ilhan Siginc , Fikrettin Sahin , Mehmet H. Ucisik , Zeynep Busra Bolat
Pancreatic cancer is a global health problem with a poor prognosis, limited treatment options and low survival rates of patients. Thus, the exploration of novel treatment approaches is crucial. Curcumin shows promise in pancreatic cancer. Curcumin has anticancer properties promoting apoptosis through the p53 pathway. However, adverse effects and low bioavailability are curcumin's main drawbacks and its delivery by nanoparticles could improve its effectiveness as a treatment option. Curcumin-loaded emulsome nanoparticles (CurEm) have shown promise in colorectal, hepatocellular, and prostate cancers. This study aims to evaluate the anticancer potential of CurEm in pancreatic cancer cell line PANC-1. The cytotoxic effects of CurEm on PANC-1 cells show cytotoxicity in dose and time-dependent manner. The selected dose 30 μM CurEm resulted spheroidal morphology in PANC-1 cells and colony forming and scratch assay conducted demonstrated significant growth inhibition and decrease in migration ability, respectively. Cell cycle analysis shows that CurEm induces G2/M arrest in PANC-1 cells. CurEm-treated PANC-1 cells showed a significant increase in p53 and Caspase 3 genes, while a significant decrease in Bcl-2 genes compared to untreated group. Western blot results showed parallel results to qPCR analysis for Bcl-2 protein levels. Interestingly, we saw low p53 protein levels in CurEm-treated PANC-1 cells. These findings shed light on the potential of CurEm as an effective and stable therapeutic approach for pancreatic cancer.
{"title":"Curcumin-loaded emulsome nanoparticles induces apoptosis through p53 signaling pathway in pancreatic cancer cell line PANC-1","authors":"Zuleyha Demirci , Zeynep Islek , Halime Ilhan Siginc , Fikrettin Sahin , Mehmet H. Ucisik , Zeynep Busra Bolat","doi":"10.1016/j.tiv.2024.105958","DOIUrl":"10.1016/j.tiv.2024.105958","url":null,"abstract":"<div><div>Pancreatic cancer is a global health problem with a poor prognosis, limited treatment options and low survival rates of patients. Thus, the exploration of novel treatment approaches is crucial. Curcumin shows promise in pancreatic cancer. Curcumin has anticancer properties promoting apoptosis through the p53 pathway. However, adverse effects and low bioavailability are curcumin's main drawbacks and its delivery by nanoparticles could improve its effectiveness as a treatment option. Curcumin-loaded emulsome nanoparticles (CurEm) have shown promise in colorectal, hepatocellular, and prostate cancers. This study aims to evaluate the anticancer potential of CurEm in pancreatic cancer cell line PANC-1. The cytotoxic effects of CurEm on PANC-1 cells show cytotoxicity in dose and time-dependent manner. The selected dose 30 μM CurEm resulted spheroidal morphology in PANC-1 cells and colony forming and scratch assay conducted demonstrated significant growth inhibition and decrease in migration ability, respectively. Cell cycle analysis shows that CurEm induces G2/M arrest in PANC-1 cells. CurEm-treated PANC-1 cells showed a significant increase in p53 and Caspase 3 genes, while a significant decrease in Bcl-2 genes compared to untreated group. Western blot results showed parallel results to qPCR analysis for Bcl-2 protein levels. Interestingly, we saw low p53 protein levels in CurEm-treated PANC-1 cells. These findings shed light on the potential of CurEm as an effective and stable therapeutic approach for pancreatic cancer.</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105958"},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142513028","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}
Pub Date : 2024-10-19DOI: 10.1016/j.tiv.2024.105955
Aizhen Li, Mingjin Yang, Wenbiao Duan, Bo Wu
In this study, MTT assays, apoptosis detection, immunofluorescence, and functional studies were used to elucidate the mechanisms underlying the effects of dihydrotanshinone I (DHT) on gastric cancer cells. Drug target prediction and analysis were conducted to identify potential targets of DHT. MTT assay revealed significant inhibition of AGS and HGC27 cells by DHT. Morphological changes, including nuclear shrinkage and the induction of necrotic cell death, were observed in DHT-treated gastric cancer cells, along with cell cycle arrest at the G2/M phase. Further analysis revealed potential targets of DHT, including PTPN11, which is highly expressed in gastric cancer cells. DHT treatment increased necrosis-related proteins (RIPK1/RIPK3/MLKL) and downregulated cell cycle-related proteins (CDC25C and CDK1) levels in gastric cancer cells. After DHT treatment, PTPN11 protein expression decreased. Furthermore, DHT significantly increased the phosphorylated p38/JNK protein level, with the phosphorylated p38 protein notably enriched in the nucleus. These functional studies indicate that PTPN11 plays a key role in mediating the effects of DHT, including cell cycle regulation and necrosis induction. In conclusion, PTPN11 is a central target through which DHT affects gastric cancer cells, regulating downstream pathways involved in necroptosis (p38/RIPK1/RIPK3/MLKL/JNK) and cell cycle arrest (p38/CDC25C/CDK1).
{"title":"Dihydrotanshinone I induces necroptosis and cell cycle arrest in gastric cancer through the PTPN11/p38 pathway","authors":"Aizhen Li, Mingjin Yang, Wenbiao Duan, Bo Wu","doi":"10.1016/j.tiv.2024.105955","DOIUrl":"10.1016/j.tiv.2024.105955","url":null,"abstract":"<div><div>In this study, MTT assays, apoptosis detection, immunofluorescence, and functional studies were used to elucidate the mechanisms underlying the effects of dihydrotanshinone I (DHT) on gastric cancer cells. Drug target prediction and analysis were conducted to identify potential targets of DHT. MTT assay revealed significant inhibition of AGS and HGC27 cells by DHT. Morphological changes, including nuclear shrinkage and the induction of necrotic cell death, were observed in DHT-treated gastric cancer cells, along with cell cycle arrest at the G2/M phase. Further analysis revealed potential targets of DHT, including PTPN11, which is highly expressed in gastric cancer cells. DHT treatment increased necrosis-related proteins (RIPK1/RIPK3/MLKL) and downregulated cell cycle-related proteins (CDC25C and CDK1) levels in gastric cancer cells. After DHT treatment, PTPN11 protein expression decreased. Furthermore, DHT significantly increased the phosphorylated p38/JNK protein level, with the phosphorylated p38 protein notably enriched in the nucleus. These functional studies indicate that PTPN11 plays a key role in mediating the effects of DHT, including cell cycle regulation and necrosis induction. In conclusion, PTPN11 is a central target through which DHT affects gastric cancer cells, regulating downstream pathways involved in necroptosis (p38/RIPK1/RIPK3/MLKL/JNK) and cell cycle arrest (p38/CDC25C/CDK1).</div></div>","PeriodicalId":54423,"journal":{"name":"Toxicology in Vitro","volume":"102 ","pages":"Article 105955"},"PeriodicalIF":2.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142481020","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}
Pub Date : 2024-10-19DOI: 10.1016/j.tiv.2024.105956
Peter Pôbiš , Tatiana Milasová , Helena Kandárová
Medical devices are integral to a wide array of medical interventions and are increasingly utilized in both clinical and home settings. Within the oral cavity, intraoral medical devices are employed for various applications, to improve quality of life and maintain oral health and hygiene. However, the dynamic and complex environment of the oral cavity, characterized by the influence of factors, such as saliva composition, fluctuating pH, and microbial flora presents a challenge to ensure the safety of end-users.
In this paper, we investigate the feasibility of utilization of 3D reconstructed human tissue models for the assessment of biocompatibility of intraoral medical devices. Building upon experiences drawn from the development and validation of ISO 10993-23 and from the development of a protocol for ocular irritation and photo-irritation, we suggest a new protocol for buccal mucosa irritation testing. The methodology is based on the viability assessment and analysis of cytokine release into media. By addressing intraoral medical devices biocompatibility testing, we aim to contribute to the advancement of biocompatibility assessment methodologies and increase the applicability of ISO 10993-23.
医疗器械是各种医疗干预措施不可或缺的一部分，在临床和家庭环境中的应用越来越广泛。在口腔内，口腔内医疗器械被用于各种应用，以提高生活质量，保持口腔健康和卫生。然而，口腔环境动态而复杂，受到唾液成分、pH 值波动和微生物菌群等因素的影响，这对确保最终用户的安全提出了挑战。在本文中，我们研究了利用三维重建人体组织模型评估口腔内医疗设备生物相容性的可行性。根据 ISO 10993-23 的开发和验证经验以及眼刺激和光刺激协议的开发经验，我们提出了一种新的颊粘膜刺激测试协议。该方法基于对细胞因子释放到介质中的活力评估和分析。通过解决口内医疗器械生物相容性测试问题，我们希望为生物相容性评估方法的进步做出贡献，并提高 ISO 10993-23 的适用性。
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