Vanadyl complexes discriminate between neuroblastoma cells and primary neurons by inducing cell-specific apoptotic pathways.

Vanadium compounds have arisen as potential therapeutic agent for the treatment of cancers over the past decades. A few studies suggested that vanadyl complexes may discriminate between the cancerous and the normal cells. Here, we reported the investigation on the pro-apoptotic effect and the underlying mechanism of bis(acetylacetonato) oxovanadium(IV) ([VO(acac)2]) on SH-SY5Y neuroblastoma cells in comparison with that of mouse primary cortex neurons. The experimental results revealed that [VO(acac)2] showed about 10-fold higher cytotoxicity (IC50 ~16 μM) on the neuroblastoma cells than on normal neurons (IC50 ~250 μM). Further analysis indicated that the vanadyl complex suppressed the growth of neuroblastoma cells via different pathways depending on its concentration. It induced a special cyclin D-mediated and p53-independent cell apoptosis at <50 μM but cell cycle arrests at >50 μM. In contrast, [VO(acac)2] promoted cell viability of primary neurons in the concentration range of 0-150 μM; while [VO(acac)2] at hundreds of μM would cause neuronal death possibly via the reactive oxygen species (ROS)-mediated signal pathways. The extraordinary discrimination between neuroblastoma cells and primary neurons suggests potential application of vanadyl complexes for therapeutic treatment of neuroblastoma. In addition, the p53-independent apoptotic pathways induced by vanadyl complexes may provide new insights for future discovery of new anticancer drugs overcoming the chemo-resistance due to p53 mutation.