Molecular Iodine/PPARγ Interaction in the Invasion and Angiogenesis of Neuroblastoma Xenografts

The study investigates the impact of molecular iodine (I₂) supplementation on the viability, invasiveness, and angiogenic potential of high-risk neuroblastoma (NB). In vitro assays were performed using NB cell lines SK-N-AS (non-MYCN-amplified) and SK-N-BE(2) (MYCN-amplified). The role of peroxisome proliferator-activated receptor gamma (PPARγ) was evaluated using the antagonist GW9662, gene expression (RT-qPCR), and protein levels (Western blot). In vivo, zebrafish xenografts were used to evaluate tumor size, angiogenesis, and caudal cell dissemination. I₂ supplementation significantly decreased cell viability in both cell lines, independent of PPARγ activation. In SK-N-BE(2), I₂ impaired cell migration, as measured by a wound-healing assay, in apparent independence of PPARγ activation. However, gene expression indicates that I₂ acts in complex ways, including direct antioxidant effects and PPARγ-mediated effects. The significant decrease in reactive oxygen species levels (DCFDA staining) and the silencing of the long noncoding RNA myocardial infarction-associated transcript (MIAT) by I₂ were directly associated with decreased MYCN and TrkB expression. In contrast, PPARγ activation was accompanied by overexpression of FasN and TrkA and a significant decrease in Aurka, a MYCN-stabilizing protein. In zebrafish, I₂-pretreated SK-N-BE(2) xenografts exhibited a clear reduction in angiogenesis (vascular density) and a decrease in invasive capacity. In conclusion, I₂ supplementation decreases cell viability and attenuates invasion and angiogenesis in NB cells, highlighting its potential as an adjuvant to conventional therapy for high-risk NB.