S. Madesh, Raghul Murugan, Avra Sau, S Jubie, Akey Krishna Swaroop, Rajakrishnan Rajagopal, Kathiravan Muthu Kumaradoss, Jesu Arockiaraj
{"title":"纳米香豆素衍生物CS-QM2抑制肿瘤生长的斑马鱼模型实验","authors":"S. Madesh, Raghul Murugan, Avra Sau, S Jubie, Akey Krishna Swaroop, Rajakrishnan Rajagopal, Kathiravan Muthu Kumaradoss, Jesu Arockiaraj","doi":"10.1002/jbt.70239","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Cancer remains a significant global health challenge with limited therapeutic success, prompting the need for innovative treatment strategies. This study investigates the anticancer potential of nano-encapsulated metal derivatives (CS-QM2) using a zebrafish model with chemically induced cellular neoplasia. Characterization of CS-QM2 nanoparticles revealed successful synthesis with a high entrapment efficiency and enhanced drug release under acidic conditions. Zebrafish embryos exposed to 7,12-Dimethylbenz[a]anthracene (DMBA) exhibited significant malformations, macrophage accumulation, and abnormal tissue growth, which were markedly reduced by CS-QM2 treatment. CS-QM2 significantly increases intracellular ROS, resulting in higher LPO and induces apoptosis in neoplasm tissues. Furthermore, CS-QM2 treatment alters the tumor microenvironment, reducing macrophage accumulation by decreasing neutral lipid droplets, disrupting TAM metabolic support and limiting their protumorigenic activities. Biochemical assays demonstrated restored activities of antioxidant enzymes SOD, CAT, and GSH. Gene expression analysis showed upregulation of apoptosis and tumor suppressor genes (<i>cas3</i>, <i>p53</i>) and downregulation of inflammatory genes (<i>cox-2</i>, <i>nf-kb</i>). Histological assessment and SEM analysis confirmed reduced neoplasm occurrence and tissue abnormalities. These findings suggest that CS-QM2 nanoparticles effectively inhibit neoplasm growth and modulate the tumor microenvironment through oxidative stress induction and gene expression regulation.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2000,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Nano-Encapsulated Coumarin Derivative, CS-QM2 Inhibits Neoplasm Growth: Experimented in Zebrafish Model\",\"authors\":\"S. Madesh, Raghul Murugan, Avra Sau, S Jubie, Akey Krishna Swaroop, Rajakrishnan Rajagopal, Kathiravan Muthu Kumaradoss, Jesu Arockiaraj\",\"doi\":\"10.1002/jbt.70239\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Cancer remains a significant global health challenge with limited therapeutic success, prompting the need for innovative treatment strategies. This study investigates the anticancer potential of nano-encapsulated metal derivatives (CS-QM2) using a zebrafish model with chemically induced cellular neoplasia. Characterization of CS-QM2 nanoparticles revealed successful synthesis with a high entrapment efficiency and enhanced drug release under acidic conditions. Zebrafish embryos exposed to 7,12-Dimethylbenz[a]anthracene (DMBA) exhibited significant malformations, macrophage accumulation, and abnormal tissue growth, which were markedly reduced by CS-QM2 treatment. CS-QM2 significantly increases intracellular ROS, resulting in higher LPO and induces apoptosis in neoplasm tissues. Furthermore, CS-QM2 treatment alters the tumor microenvironment, reducing macrophage accumulation by decreasing neutral lipid droplets, disrupting TAM metabolic support and limiting their protumorigenic activities. Biochemical assays demonstrated restored activities of antioxidant enzymes SOD, CAT, and GSH. Gene expression analysis showed upregulation of apoptosis and tumor suppressor genes (<i>cas3</i>, <i>p53</i>) and downregulation of inflammatory genes (<i>cox-2</i>, <i>nf-kb</i>). Histological assessment and SEM analysis confirmed reduced neoplasm occurrence and tissue abnormalities. These findings suggest that CS-QM2 nanoparticles effectively inhibit neoplasm growth and modulate the tumor microenvironment through oxidative stress induction and gene expression regulation.</p></div>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"39 4\",\"pages\":\"\"},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2025-03-27\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biochemical and Molecular Toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70239\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biochemical and Molecular Toxicology","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/jbt.70239","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Nano-Encapsulated Coumarin Derivative, CS-QM2 Inhibits Neoplasm Growth: Experimented in Zebrafish Model
Cancer remains a significant global health challenge with limited therapeutic success, prompting the need for innovative treatment strategies. This study investigates the anticancer potential of nano-encapsulated metal derivatives (CS-QM2) using a zebrafish model with chemically induced cellular neoplasia. Characterization of CS-QM2 nanoparticles revealed successful synthesis with a high entrapment efficiency and enhanced drug release under acidic conditions. Zebrafish embryos exposed to 7,12-Dimethylbenz[a]anthracene (DMBA) exhibited significant malformations, macrophage accumulation, and abnormal tissue growth, which were markedly reduced by CS-QM2 treatment. CS-QM2 significantly increases intracellular ROS, resulting in higher LPO and induces apoptosis in neoplasm tissues. Furthermore, CS-QM2 treatment alters the tumor microenvironment, reducing macrophage accumulation by decreasing neutral lipid droplets, disrupting TAM metabolic support and limiting their protumorigenic activities. Biochemical assays demonstrated restored activities of antioxidant enzymes SOD, CAT, and GSH. Gene expression analysis showed upregulation of apoptosis and tumor suppressor genes (cas3, p53) and downregulation of inflammatory genes (cox-2, nf-kb). Histological assessment and SEM analysis confirmed reduced neoplasm occurrence and tissue abnormalities. These findings suggest that CS-QM2 nanoparticles effectively inhibit neoplasm growth and modulate the tumor microenvironment through oxidative stress induction and gene expression regulation.
期刊介绍:
The Journal of Biochemical and Molecular Toxicology is an international journal that contains original research papers, rapid communications, mini-reviews, and book reviews, all focusing on the molecular mechanisms of action and detoxication of exogenous and endogenous chemicals and toxic agents. The scope includes effects on the organism at all stages of development, on organ systems, tissues, and cells as well as on enzymes, receptors, hormones, and genes. The biochemical and molecular aspects of uptake, transport, storage, excretion, lactivation and detoxication of drugs, agricultural, industrial and environmental chemicals, natural products and food additives are all subjects suitable for publication. Of particular interest are aspects of molecular biology related to biochemical toxicology. These include studies of the expression of genes related to detoxication and activation enzymes, toxicants with modes of action involving effects on nucleic acids, gene expression and protein synthesis, and the toxicity of products derived from biotechnology.