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

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 µM 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.

Monensin, an Antibiotic Isolated from Streptomyces Cinnamonensis, Regulates Human Neuroblastoma Cell Proliferation via the PI3K/AKT Signaling Pathway and Acts Synergistically with Rapamycin.

Neuroblastoma is the most common extracranial childhood tumor and accounts for approximately 15% of pediatric cancer-related deaths. Further studies are needed to identify potential therapeutic targets for neuroblastoma. Monensin is an ionophore antibiotic obtained from Streptomyces cinnamonensis with known antibacterial and antiparasitic effects. No study has reported the effects of monensin on SH-SY5Y neuroblastoma cells by targeting the PI3K/AKT signaling pathway. The aim of this study was to investigate the antiproliferative effects of monensin alone and in combination with rapamycin in human SH-SY5Y neuroblastoma cells mediated by the PI3K/AKT signaling pathway. The effects of single and combination applications of monensin and rapamycin on SH-SY5Y cell proliferation were investigated by XTT, and their effects on the PI3K/AKT signaling pathway by RT-PCR, immunohistochemistry, immunofluorescence, and Western blotting. The combined effects of monensin and rapamycin on SH-SY5Y proliferation were most potent at 72 h (combination index < 1). The combination of monensin and rapamycin caused a significant decrease in the expression of P21RAS, AKT, and MAPK1 genes. Single and combined administrations of monensin and rapamycin caused a significant decrease in PI3K/AKT expression. Our results showed for the first time that monensin exerts an antiproliferative effect by targeting the PI3K/AKT signaling pathway in neuroblastoma cells. It is suggested that monensin and its combination with rapamycin may be an effective therapeutic candidate for treating neuroblastoma.

Uridine treatment protects against neonatal brain damage and long-term cognitive deficits caused by hyperoxia.

Exposure to excessive oxygen in survivors of preterm birth is one of the factors that underlie the adverse neurological outcome in later life. Various pathological changes including enhanced apoptotic activity, oxidative stress and inflammation as well as decreased neuronal survival has been demonstrated in animal models of neonatal hyperoxia. The aim of the present study was to investigate the effect of administering uridine, an anti-apoptotic agent, on cellular, molecular and behavioral consequences of hyperoxia-induced brain damage in a neonatal rat model. For five days from birth, rat pups were either subjected continuously to room air (21% oxygen) or hyperoxia (80% oxygen) and received daily intraperitoneal (i.p.) injections of saline (0.9% NaCl) or uridine (500mg/kg). Two-thirds of all pups were sacrificed on postnatal day 5 (P5) in order to investigate apoptotic cell death, myelination and number of surviving neurons. One-thirds of pups were raised through P40 in order to evaluate early reflexes, sensorimotor coordination and cognitive functions followed by investigation of neuron count and myelination. We show that uridine treatment reduces apoptotic cell death and hypomyelination while increasing the number of surviving neurons in hyperoxic pups on P5. In addition, uridine enhances learning and memory performances in periadolescent rats on P40. These data suggest that uridine administered during the course of hyperoxic insult enhances cognitive functions at periadolescent period probably by reducing apoptotic cell death and preventing hypomyelination during the neonatal period in a rat model of hyperoxia-induced brain injury.