Neuroblastoma, cancer mostly affecting children, consists of undifferentiated neural crest cells in the spinal cord and adrenal medulla that proliferate uncontrollably. Current treatment involves retinoic acid as maintenance therapy. Research is ongoing to see if retinoic acid can be used in combination with other drugs. Drug X, a myosin inhibitor and drug Y, a sigma-1 receptor agonist, have not been tested together with retinoic acid and this project’s aim was to test how these drugs affect neuroblastoma cells. Proliferation assay was performed on neuroblastoma cells lines treated with drug X, drug Y and retinoic acid. Reverse transcription with quantitative polymerase chain reaction was used to measure the expression of the genes tyrosine hydroxylase, neurofilament 200, novel calcium channel, sigma-1-receptor and novel long non-coding RNA. Live cell imaging of mitochondria and calcium ions were performed for cells treated with retinoic acid and drug Y. Proliferation of cells using different concentrations of drug Y showed no significant difference with control over a 72 h test period. High concentration of drug Y showed a significant decrease in proliferation compared with control after 72 h, while drug Y + drug X showed an even more significant decrease in proliferation. Retinoic acid +drug Y showed a significant increase in gene expression for novel calcium channel and tyrosine hydroxylase and higher calcium ion activity. The combination treatments seem to work synergistically and enhance the expression of some important genes involved in differentiation of neuroblastoma cell lines. However, more tests are needed to validate the results.