International Journal of Hematology and Oncology 2019, Vol 29, Num 2 Page(s): 070-078
Betulinic Acid and Cisplatin Inhibit Metastasis Related Genes in Neuroblastoma Cells Due to Their N-MYC Status

Serdar BAYRAK1, Zekiye ALTUN2, Dilek INCE3, Safiye AKTAS2, Nur OLGUN3

1Dokuz Eylul University, Institute of Oncology, Department of Clinical Oncology, Izmir, TURKEY
2Dokuz Eylul University, Institute of Oncology, Department of Basic Oncology, Izmir, TURKEY
3Dokuz Eylul University, Institute of Oncology, Department of Pediatric Oncology, Izmir, TURKEY

Keywords: Betulinic acid, N-MYC, Metastases genes, Neuroblastoma, Cisplatin
Betulinic acid-(BA) has apoptotic effects on neuroblastoma. This study explored the effects of cisplatin-(CP), BA and combination of BA and CP (BA-CP) on cell proliferation, apoptotic cell death and expressions of metastasis related genes in neuroblastoma. In this study, N-MYC positive and negative neuroblastoma cell lines, KELLY and SHSY5Y, were treated with BA, CP and BA-CP combinations. BA-CP combinations showed synergistic activity on cell growth inhibition and apoptotic cell death in both neuroblastoma cell lines. In SHSY5Y cells BA, CP or BA-CP treatments induced downregulation most of the metastatic genes’ expressions. In KELLY cells, while CP treatment decreased some metastatic gene expressions, BA or BA-CP treatment reduced only DENR and RB1. BA and BA-CP showed prominent effect on metastasis related gene expressions in predominantly KELLY cells. The results of this study suggest that BA may be a promising anti-cancer agent for neuroblastoma treatment, whereas CP is still the most suitable chemotherapeutic drug for aggressive neuroblastoma.