Insights from an in vitro study: the anti-proliferative effects of indole-3-acetic acid in neuroblastoma cells

Indole-3-acetic acid (IAA) is a natural indole derivative found in fruits and vegetables, known for its pharmacological properties, including anticancer activity. Neuroblastomas (NB) are the most common extracranial tumors in children, accounting for approximately 10% of all pediatric malignancies. Around half of NB cases are associated with gain-of-function mutations in the ALK gene. In this study, we selected the SH-SY5Y cell line as an in vitro model of human neuroblastoma to investigate the potential use of IAA as an effective anti-proliferative agent. First, we examined the effects of IAA on SH-SY5Y cells and, in parallel, on non-cancerous ARPE-19 retinal pigment epithelial cells, assessing cell viability. We found that IAA treatment consistently reduced cell viability in SH-SY5Y cells. This reduction in viability was accompanied by a stronger inhibition of ALK expression in SH-SY5Y cells compared to ARPE-19 cells. Next, we evaluated the impact of IAA treatment on cell cycle progression and autophagy. Our results revealed that IAA induces a dose-dependent G1 arrest within 24 h of exposure and upregulates key autophagy-related proteins in SH-SY5Y cells. Additionally, IAA treatment inhibited colony formation and cell migration in SH-SY5Y cells, even at the lowest concentration. Altogether, our findings indicate that IAA exerts anti-proliferative effects on neuroblastoma cells by inhibiting cell viability and ALK expression, cell cycle progression, and suppressing colony formation and migration, with minimal impact on non-cancerous ARPE-19 cells. However, additional mechanisms may contribute to its activity. Further studies in different cellular contexts are needed to clarify its clinical potential and therapeutic relevance in cancer treatment.