Investigation of the anticancer mechanism of monensin via apoptosis-related factors in SH-SY5Y neuroblastoma cells

Abstract

Monensin is an ionophore antibiotic that inhibits the growth of cancer cells. The aim of this study was to investigate the apoptosis-mediated anticarcinogenic effects of monensin in SH-SY5Y neuroblastoma cells. The effects of monensin on cell viability, invasion, migration, and colony formation were determined by XTT, matrigel-chamber, wound healing, and colony formation tests, respectively. The effects of monensin on apoptosis were determined by real-time polymerase chain reaction, TUNEL, Western blot, and Annexin V assay. We have shown that monensin suppresses neuroblastoma cell viability, invasion, migration, and colony formation. Moreover, we reported that monensin inhibits cell viability by triggering apoptosis of neuroblastoma cells. Monensin caused apoptosis by increasing caspase-3, 7, 8, and 9 expressions and decreasing Bax and Bcl-2 expressions in neuroblastoma cells. In Annexin V results, the rates of apoptotic cells were found to be 9.66 +/- 0.01% (p < 0.001), 29.28 +/- 0.88% (p < 0.01), and 62.55 +/- 2.36% (p < 0.01) in the 8, 16, and 32 mu M monensin groups, respectively. In TUNEL results, these values were, respectively; 35 +/- 2% (p < 0.001), 34 +/- 0.57% (p < 0.001), and 75 +/- 2.51% (p < 0.001). Our results suggest that monensin may be a safe and effective therapeutic candidate for treating pediatric neuroblastoma. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Neuroblastoma is the most common extracranial childhood tumor originating from neural crest cells. Neuroblastomas constitute similar to 15% of childhood cancer deaths. There is a need to develop new and alternative advanced treatment approaches for neuroblastoma oncogenesis. Monensin is an ionophore antibiotic with antiparasitic and antibacterial effects. WHAT QUESTION DID THIS STUDY ADDRESS? No study has been found on the anticancer properties of monensin on neuroblastoma cell proliferation, migration, invasion, and apoptosis. This study addresses dose-dependent and apoptotic pathway-mediated anticarcinogenic properties of monensin in neuroblastoma cells in vitro. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? Monensin suppresses neuroblastoma cell proliferation, invasion, migration, and colony formation. Monensin triggers apoptosis by increasing caspase-3, 7, 8, 9, and cleaved-PARP1 expressions and decreasing Bax and Bcl-2 expressions. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? Monensin may be a safe and effective therapeutic drug candidate in the treatment of pediatric neuroblastoma.