The effects of indole-2,3-dione on radiosensitivity of U251 cells and zebrafish embryos

Abstract

Radiotherapy is an effective treatment for gliomas, which are among the most malignant tumors in the central nervous system (CNS). A significant challenge in glioma radiotherapy is improving tumor control while minimizing damage to normal nervous tissue. In this study, we investigated the dual role of indole-2,3-dione (Isatin, ISA), a compound with diverse biological and pharmacological activities, including anticancer, antioxidant, and anti-inflammatory properties, in modulating radiosensitivity. The effects of ISA were examined in both human malignant glioblastoma U251 cells in vitro and zebrafish (Danio rerio) embryos in vivo. In U251 cells, irradiation significantly decreased cell viability and clonogenic capacity, while increasing reactive oxygen species (ROS) levels, inducing Cell cycle G2/M arrest, upregulating apoptotic gene expression, and inducing apoptosis. ISA pretreatment markedly enhanced these radiation-induced effects, potentiating clonogenic inhibition and proapoptotic activity. Moreover, combined ISA and irradiation treatment led to increased DNA damage and delayed DNA repair in U251 cells. In the in vivo zebrafish model, ISA pretreatment demonstrated significant radioprotective effects, reducing radiation-induced damage, including embryo mortality, behavioral alterations, ROS overproduction, and upregulation of proapoptotic genes. These findings suggest that ISA has dual functionality: acting as a radiosensitizer for glioblastoma cells and a radioprotector for normal CNS cells, primarily by modulating ROS production and apoptotic pathways. This study provides robust preclinical evidence supporting the potential clinical application of ISA in brain tumor radiotherapy, offering a promising approach to optimize therapeutic outcomes in glioma treatment.