{"title":"橄榄苦苷通过下调HIF-1α促进前列腺癌细胞DNA损伤。","authors":"Hanping Wei, Haoran Wu, Wei Feng","doi":"10.1002/jbt.70524","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>This study aimed to investigate the effects of oleuropein (Ole) on prostate cancer (PCa) cells and its underlying mechanisms, particularly whether it mediates DNA damage through HIF-1α. PCa cells DU145 were treated with different concentrations of Ole (25, 50, 100, 250, and 500 μM) or transfected with HIF-1α overexpression plasmid. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the cell viability; flow cytometry was used to detect apoptosis; quantitative reverse transcription polymerase chain reaction and western blot were employed to measure HIF-1α expression levels. Additionally, comet assay and western blot were employed to evaluate DNA damage and the expression of DNA damage-related proteins (γH2AX and p53). Ole significantly inhibited DU145 cell viability in a concentration-dependent manner (<i>p</i> < 0.01). Additionally, apoptosis rates increased significantly with increasing Ole concentrations (<i>p</i> < 0.01). Ole induced DNA damage in DU145 cells. Notably, overexpression of HIF-1α partially reversed the effects of Ole on PCa cells. Ole inhibits DU145 cell viability, promotes apoptosis, and induces DNA damage, possibly through the HIF-1α pathway. HIF-1α plays a potential role in the anticancer effects of Ole, providing new experimental evidence for its application in PCa research.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8000,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Oleuropein Promotes DNA Damage in Prostate Cancer Cells via HIF-1α Downregulation\",\"authors\":\"Hanping Wei, Haoran Wu, Wei Feng\",\"doi\":\"10.1002/jbt.70524\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>This study aimed to investigate the effects of oleuropein (Ole) on prostate cancer (PCa) cells and its underlying mechanisms, particularly whether it mediates DNA damage through HIF-1α. PCa cells DU145 were treated with different concentrations of Ole (25, 50, 100, 250, and 500 μM) or transfected with HIF-1α overexpression plasmid. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the cell viability; flow cytometry was used to detect apoptosis; quantitative reverse transcription polymerase chain reaction and western blot were employed to measure HIF-1α expression levels. Additionally, comet assay and western blot were employed to evaluate DNA damage and the expression of DNA damage-related proteins (γH2AX and p53). Ole significantly inhibited DU145 cell viability in a concentration-dependent manner (<i>p</i> < 0.01). Additionally, apoptosis rates increased significantly with increasing Ole concentrations (<i>p</i> < 0.01). Ole induced DNA damage in DU145 cells. Notably, overexpression of HIF-1α partially reversed the effects of Ole on PCa cells. Ole inhibits DU145 cell viability, promotes apoptosis, and induces DNA damage, possibly through the HIF-1α pathway. HIF-1α plays a potential role in the anticancer effects of Ole, providing new experimental evidence for its application in PCa research.</p></div>\",\"PeriodicalId\":15151,\"journal\":{\"name\":\"Journal of Biochemical and Molecular Toxicology\",\"volume\":\"39 10\",\"pages\":\"\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-30\",\"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.70524\",\"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.70524","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Oleuropein Promotes DNA Damage in Prostate Cancer Cells via HIF-1α Downregulation
This study aimed to investigate the effects of oleuropein (Ole) on prostate cancer (PCa) cells and its underlying mechanisms, particularly whether it mediates DNA damage through HIF-1α. PCa cells DU145 were treated with different concentrations of Ole (25, 50, 100, 250, and 500 μM) or transfected with HIF-1α overexpression plasmid. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the cell viability; flow cytometry was used to detect apoptosis; quantitative reverse transcription polymerase chain reaction and western blot were employed to measure HIF-1α expression levels. Additionally, comet assay and western blot were employed to evaluate DNA damage and the expression of DNA damage-related proteins (γH2AX and p53). Ole significantly inhibited DU145 cell viability in a concentration-dependent manner (p < 0.01). Additionally, apoptosis rates increased significantly with increasing Ole concentrations (p < 0.01). Ole induced DNA damage in DU145 cells. Notably, overexpression of HIF-1α partially reversed the effects of Ole on PCa cells. Ole inhibits DU145 cell viability, promotes apoptosis, and induces DNA damage, possibly through the HIF-1α pathway. HIF-1α plays a potential role in the anticancer effects of Ole, providing new experimental evidence for its application in PCa research.
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.