{"title":"碘- δ内酯抑制人HT29结肠癌异种移植血管生成。","authors":"Romina Oglio , Federico Buschittari , Leonardo Salvarredi , Jennifer Michaux , Carla Rodriguez , Marina Perona , Alejandra Dagrosa , Guillermo Juvenal , Lisa Thomasz","doi":"10.1016/j.plefa.2022.102507","DOIUrl":null,"url":null,"abstract":"<div><h3>Introduction</h3><p>Several studies have shown the antiproliferative effect of iodine and 5‑hydroxy-6 iodo-eicosatrienoic delta lactone (IL-δ) on diverse tissues. It was demonstrated that molecular iodine (I<sub>2</sub>) and IL-δ, but not iodide (<em>I</em><sup>−</sup>), exerts anti-neoplastic actions in different cancers. The underlying mechanism through which IL-δ inhibits tumor growth remains unclear. The aim of this study was to analyze the effect of IL-δ on tumor growth and angiogenesis in human HT29 colorectal cancer xenografts.</p></div><div><h3>Methodology and Results</h3><p>HT29 cells were injected subcutaneously into the flanks of nude mice and IL-δ was i.p. injected at a dose of 15 μg three days a week. IL-δ treatment in HT29 xenografts showed time-dependent inhibition of tumor growth, decrease of mitosis and PCNA expression (<em>p</em> < 0.05), increase of P27 expression and Caspase 3 activity after 18 days of treatment (<em>p</em> < 0.05). To assess tumor Microvessel Densities (MVD), CD31 staining by immunohistochemistry was analyzed. IL-δ treatment decreased MVD by 17% and 30% after 18 and 30 days respectively (<em>p</em> < 0.05), as well as it decreased VEGF and VEGF-R2 expression (<em>p</em> < 0.05). Additionally, our findings demonstrated that IL-δ increased VEGF-R1 and Ang-1 mRNA levels (<em>p</em> < 0.01).</p></div><div><h3>Conclusion</h3><p>The antitumor efficacy of IL-δ in vivo involves inhibition of cell proliferation as well as induction of apoptosis. IL-δ has also anti-angiogenic effect associated with VEGF and VEGF-R2 downregulation followed by Ang-1 and VEGF-R1 increased expression. High levels of Ang-1 would contribute to mature vessel stabilization and maintenance while VEGF-R1 increase would produce anti-proliferative effect on endothelial cells.</p></div>","PeriodicalId":94179,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":null,"pages":null},"PeriodicalIF":3.0000,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"6 Iodo-delta lactone inhibits angiogenesis in human HT29 colon adenocarcinoma xenograft.\",\"authors\":\"Romina Oglio , Federico Buschittari , Leonardo Salvarredi , Jennifer Michaux , Carla Rodriguez , Marina Perona , Alejandra Dagrosa , Guillermo Juvenal , Lisa Thomasz\",\"doi\":\"10.1016/j.plefa.2022.102507\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Introduction</h3><p>Several studies have shown the antiproliferative effect of iodine and 5‑hydroxy-6 iodo-eicosatrienoic delta lactone (IL-δ) on diverse tissues. It was demonstrated that molecular iodine (I<sub>2</sub>) and IL-δ, but not iodide (<em>I</em><sup>−</sup>), exerts anti-neoplastic actions in different cancers. The underlying mechanism through which IL-δ inhibits tumor growth remains unclear. The aim of this study was to analyze the effect of IL-δ on tumor growth and angiogenesis in human HT29 colorectal cancer xenografts.</p></div><div><h3>Methodology and Results</h3><p>HT29 cells were injected subcutaneously into the flanks of nude mice and IL-δ was i.p. injected at a dose of 15 μg three days a week. IL-δ treatment in HT29 xenografts showed time-dependent inhibition of tumor growth, decrease of mitosis and PCNA expression (<em>p</em> < 0.05), increase of P27 expression and Caspase 3 activity after 18 days of treatment (<em>p</em> < 0.05). To assess tumor Microvessel Densities (MVD), CD31 staining by immunohistochemistry was analyzed. IL-δ treatment decreased MVD by 17% and 30% after 18 and 30 days respectively (<em>p</em> < 0.05), as well as it decreased VEGF and VEGF-R2 expression (<em>p</em> < 0.05). Additionally, our findings demonstrated that IL-δ increased VEGF-R1 and Ang-1 mRNA levels (<em>p</em> < 0.01).</p></div><div><h3>Conclusion</h3><p>The antitumor efficacy of IL-δ in vivo involves inhibition of cell proliferation as well as induction of apoptosis. IL-δ has also anti-angiogenic effect associated with VEGF and VEGF-R2 downregulation followed by Ang-1 and VEGF-R1 increased expression. High levels of Ang-1 would contribute to mature vessel stabilization and maintenance while VEGF-R1 increase would produce anti-proliferative effect on endothelial cells.</p></div>\",\"PeriodicalId\":94179,\"journal\":{\"name\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.0000,\"publicationDate\":\"2022-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins, leukotrienes, and essential fatty acids\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0952327822001193\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins, leukotrienes, and essential fatty acids","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0952327822001193","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
6 Iodo-delta lactone inhibits angiogenesis in human HT29 colon adenocarcinoma xenograft.
Introduction
Several studies have shown the antiproliferative effect of iodine and 5‑hydroxy-6 iodo-eicosatrienoic delta lactone (IL-δ) on diverse tissues. It was demonstrated that molecular iodine (I2) and IL-δ, but not iodide (I−), exerts anti-neoplastic actions in different cancers. The underlying mechanism through which IL-δ inhibits tumor growth remains unclear. The aim of this study was to analyze the effect of IL-δ on tumor growth and angiogenesis in human HT29 colorectal cancer xenografts.
Methodology and Results
HT29 cells were injected subcutaneously into the flanks of nude mice and IL-δ was i.p. injected at a dose of 15 μg three days a week. IL-δ treatment in HT29 xenografts showed time-dependent inhibition of tumor growth, decrease of mitosis and PCNA expression (p < 0.05), increase of P27 expression and Caspase 3 activity after 18 days of treatment (p < 0.05). To assess tumor Microvessel Densities (MVD), CD31 staining by immunohistochemistry was analyzed. IL-δ treatment decreased MVD by 17% and 30% after 18 and 30 days respectively (p < 0.05), as well as it decreased VEGF and VEGF-R2 expression (p < 0.05). Additionally, our findings demonstrated that IL-δ increased VEGF-R1 and Ang-1 mRNA levels (p < 0.01).
Conclusion
The antitumor efficacy of IL-δ in vivo involves inhibition of cell proliferation as well as induction of apoptosis. IL-δ has also anti-angiogenic effect associated with VEGF and VEGF-R2 downregulation followed by Ang-1 and VEGF-R1 increased expression. High levels of Ang-1 would contribute to mature vessel stabilization and maintenance while VEGF-R1 increase would produce anti-proliferative effect on endothelial cells.