Abstract A057 Molecular iodine reduces the invasiveness of neuroblastoma xenografts in zebrafish

Abstract Neuroblastoma (NB) is one of childhood´s most common extra-cranial solid tumors, with 90 % of the cases occurring in those <5 years of age. NB is highly heterogeneous, with variable biological and clinical characteristics; it exhibits spontaneous or induced regression processes (low-risk NB) up to highly invasive capacities and drug-resistance tumors (high-risk NB). High-risk NB overexpresses the N-MYC gene associated with invasion and chemoresistance. On the other hand, molecular iodine (I2) exerts antiproliferative and differentiation effects on cancer cells. Our previous studies have shown that I2 synergizes the neurodifferentiator effect of all-trans-retinoic acid in low-risk (SN-K-AS) and the antiproliferative and apoptotic action of cyclophosphamide in high-risk (SK-N-BE2) neuroblastoma cell lines. The cellular mechanisms include the activation of antioxidant pathways (Nrf2) and the overexpression of the peroxisome proliferator-activated receptor gamma (PPARγ). I2 can exert its effects through the activation of PPARγ, and this in turn downregulates the expression of chemoresistance genes (TrkB, MDR1, N-MYC). The aim of the present work is to analyze the effect of I2 on the invasive capacity of SK-N-BE2 both in vitro (wound healing assay) and in vivo (zebrafish model). NB cells were cultured in DMEM/F12 (1:1) medium with and without I2 400 mM for 96 hours. Wound assay was analyzed after 24 hours, whereas 400 to 600 cells labeled with Fast DiI (4 mg/mL) were injected into the perivitelline space of zebrafish larvae 2 days post fertilization. Cancer cell dissemination to the caudal vein plexus was analyzed with a fluorescence Nikon Eclipse E-600 microscope (10X/0.30 magnification) after 72 hours. Data show that I2-pretreated SK-N-BE2 cells exhibit a decrease in migration capacity in vitro (control 59.5 ± 8.5, I2 65.0± 9.4 p<0.6) and a clear and significant inhibition in vivo (control 7.6 ± 4.6, I2 4.8± 3.8 p< 0.0015). Analysis of the genetic expression (qRT-PCR) shows that I2 induces PPARγ and decreases N-MYC and TrkB expression through an apparent PPARγ independent pathway at 96 hours. The establishment of NB PPARγ knock-out cells and evaluation of the I2 effect in tumoral angiogenesis on transgenic zebrafish (Fli1: EGFP) is currently under progress. Acknowledgments The authors are grateful for the technical support of Luis Roberto Rodríguez Ortiz, Nydia Hernandez Ríos, and Martín García Servín. This work was supported by PAPIIT-UNAM IN202322, and CONAHCYT scholarship 862245. Citation Format: Edgar R. Juvera-Avalos, Gustavo Orizaga-Osti, Evangelina Delgado-González, Carmen Aceves. Molecular iodine reduces the invasiveness of neuroblastoma xenografts in zebrafish [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr A057.