Isatin inhibits the invasion and metastasis of SH‑SY5Y neuroblastoma cells in vitro and in vivo

Abstract

Indoline-2,3-dione or indole-1H-2,3-dione, commonly known as isatin, is found in plants of genus Isatin and in Couropita guianancis aubl, and inhibits tumor cell proliferation through its antioxidant effects. The present study analyzed the effect of isatin on the malignant phenotype of neuroblastoma cells, and reported that isatin significantly inhibited neuroblastoma cell proliferation, invasion and migration in vitro in a dose-dependent manner, and distant metastasis in tumor-bearing mice. Mechanistically, isatin inhibited lysine-specific histone demethylase (LSD)1 and reversed the blockade on p53, thereby activating the apoptotic pathway. The inhibitory effect of isatin on LSD1 may be mediated via direct binding and molecular docking or indirectly through the TGFβ/ERK/NF-κB signaling pathway. Isatin also alleviated the renal and hepatic toxicity of cyclophosphamide in the tumor-bearing mice, indicating its potential as a candidate drug as well as an adjuvant for treating metastatic neuroblastoma.