Neuroblastoma is one of the most common extracranial solid
cancers found in young children. The prognosis of
neuroblastoma patients in advanced stages having N-myc amplification remains poor despite intensive multimodal
therapy. Agents that trigger
neuroblastoma cells to undergo cellular differentiation and thereby stop proliferation have attracted considerable interest as an alternative
therapy.
Tryptanthrin (12-dihydro-6,12-dioxoindolo-(2,1-b)-quinazoline) is a weakly basic
alkaloid isolated from the dried roots of medicinal
indigo plants known as
Banlangen. It has been shown to possess various
biological activities, such as anti-microbial, anti-inflammatory and anti-
tumor activities. However, its effects and mechanism(s) of action on human
neuroblastoma cells remain poorly understood. Therefore, the objective of this study is to investigate the effects of
tryptanthrin on the growth and differentiation of human
neuroblastoma LA-N-1 cells with N-myc amplification. Our results show that
tryptanthrin inhibited the growth of the human
neuroblastoma cells in a dose- and time-dependent manner. Mechanistic studies indicated that
tryptanthrin induced cell cycle arrest of the human
neuroblastoma LA-N-1 cells at the G0/G1 phase.
Tryptanthrin also induced neuronal differentiation of LA-N-1 cells, as assessed by morphological criteria, enhancement of
acetylcholine esterase activity and up-regulation of various
differentiation markers. Moreover,
tryptanthrin treatment led to the significant reduction of N-myc expression in LA-N-1 cells while
siRNA directed against N-myc induced morphological differentiation of LA-N-1 cells. These results, when taken together, suggest that
tryptanthrin suppressed the growth and induced neuronal differentiation in the human
neuroblastoma LA-N-1 cells and might be exploited as a potential therapeutic candidate for the treatment of high-risk
neuroblastomas with N-myc-amplification.