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6 Iodo-delta lactone inhibits angiogenesis in human HT29 colon adenocarcinoma xenograft.

Published:October 07, 2022DOI:https://doi.org/10.1016/j.plefa.2022.102507

      Highlights

      • IL-δ inhibits cell proliferation and induces apoptosis in human HT29 colon adenocarcinoma xenograft.
      • IL-δ has an anti angiogenic effect in colorectal cancer tumor vasculature.
      • The anti angiogenic effect of IL-δ involves a downregulation of VEGF and VEGF-R2 with an increased expression of Ang-1 and VEGF R1.

      Abstract

      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.

      Keywords

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