A synthetic analog of verbenachalcone potentiates NGF-induced neurite outgrowth and enhances cell survival in neuronal cell models.

Abstract

This study uses NeuroScreen-1 (NS-1) cells, a derivative of pheochromocytoma (PC12) cells, to examine neurite outgrowth induced by a novel synthetic verbenachalcone derivative, DSRB20-022 (C22). We treated NS-1 cells with varying concentrations of C22 in the presence of 2ng/mL nerve growth factor (NGF). A dose-dependent effect of C22 was observed at concentrations of 2microM and above, resulting in significant enhancement of NGF-dependent neurite outgrowth in NS-1 cells. C22 did not exhibit neuritogenic activity in the absence of NGF, but promoted a concentration-dependent increase in neurite-bearing cells without inducing cytotoxicity. Cell viability assays showed that C22 and the parent compound verbenachalcone (VC) are neuroprotective and enhanced survival of NS-1, PC12, and the murine neuro-2A (N2a) cell lines under conditions of serum deprivation. The results show that augmentation of NGF-induced neurite outgrowth by C22 in NS-1 was dependent on MAP kinase. Furthermore, the neuroprotective function of C22 and VC was accompanied by suppression of caspase-3/7 activation. However, C22 and VC exerted their antagonistic effects on caspase-3/7 activation through potentially different mechanisms of action.

• Authors: Ceiléssia M Clement, Srinivasa R Dandepally, Alfred L Williams, Gordon C Ibeanu
• Journal: Neuroscience letters (Neurosci Lett) Vol. 459 Issue 3 Pg. 157-61 (Aug 14 2009) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 19427363 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Ac-aspartyl-glutamyl-valyl-aspartyl-aminomethylcoumarin
• Butadienes
• Chalcones
• Coumarins
• DSRB20-022
• Enzyme Inhibitors
• Neuroprotective Agents
• Nitriles
• Oligopeptides
• U 0126
• verbenachalcone
• Nerve Growth Factor
• Extracellular Signal-Regulated MAP Kinases
• CASP3 protein, human
• Casp3 protein, mouse
• Casp3 protein, rat
• Casp7 protein, mouse
• Caspase 3
• Caspase 7

Topics

• Animals
• Butadienes (administration & dosage)
• Caspase 3 (metabolism)
• Caspase 7 (metabolism)
• Cell Line
• Cell Line, Tumor
• Cell Survival (drug effects, physiology)
• Chalcones (administration & dosage, chemistry)
• Coumarins (metabolism)
• Dose-Response Relationship, Drug
• Enzyme Activation (drug effects)
• Enzyme Inhibitors (administration & dosage)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors)
• Mice
• Nerve Growth Factor (metabolism)
• Neurites (drug effects, physiology)
• Neuroprotective Agents (administration & dosage, chemistry)
• Nitriles (administration & dosage)
• Oligopeptides (metabolism)
• Rats