Neuroblastoma cell lines treated with berberine induced neuronal differentiation, inhibited proliferation, restored tumor suppressor proteins, increased epithelial markers and reverted mesenchymal markers. It instigated reversal of EMT by downregulating PI3/Akt and RAS-Raf-ERK signaling, and upregulating p38-MAPK. It also modulated TGF-β receptors II and III. The gene discussed is PI3; the disease is neuroblastoma.