Cucurbitacin B inhibits growth and induces apoptosis through the JAK2/STAT3 and MAPK pathways in SH-SY5Y human neuroblastoma cells

Cucurbitacin B (CuB) is a tetracyclic triterpene that is contained in extracts from cucurbitaceous plants and has been demonstrated to have anticancer and anti-inflammatory activities. The purpose of the present study was to determine whether CuB exhibits anticancer effects on SH-SY5Y human neuroblastoma cells and to analyze the underlying molecular mechanism. The results demonstrated that CuB not only induced cell cycle arrest at the G2/M phase, but also induced apoptosis as characterized by positive Annexin V staining, downregulation of phospho-Janus kinase 2 (p-JAK2), phospho-signal transducer and activator of transcription 3 (p-STAT3), phospho-extracellular signal-regulated kinases and the activation of c-Jun N-terminal kinase and p38 mitogen activated protein kinase (MAPK). CuB also altered the expression of gene products that mediated cell proliferation (Cyclin B1 and cyclin-dependent kinase 1), cell survival (B-cell lymphoma 2, Bcl2-associated X protein) and increased the expression of p53 and p21. These results provide the evidence that JAK2/STAT3 and MAPKs have crucial roles in CuB-induced growth inhibition and apoptosis in SH-SY5Y human neuroblastoma cells.