A synthetic analog of verbenachalcone potentiates NGF-induced neurite outgrowth and enhances cell survival in neuronal cell models.
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.
Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, NC 27707, USA.
Ceiléssia M
CM
Clement
Srinivasa R
SR
Dandepally
Alfred L
AL
Williams
Gordon C
GC
Ibeanu
D000818:Animals; D002070:Butadienes / Q000008:administration & dosage; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects* / Q000502:physiology; D047188:Chalcones / Q000008:administration & dosage* / Q000737:chemistry; D003374:Coumarins / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors; D051379:Mice; D020932:Nerve Growth Factor / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000737:chemistry; D009570:Nitriles / Q000008:administration & dosage; D009842:Oligopeptides / Q000378:metabolism; D051381:Rats
C112287:Ac-aspartyl-glutamyl-valyl-aspartyl-aminomethylcoumarin; D002070:Butadienes; D047188:Chalcones; D003374:Coumarins; C543016:DSRB20-022; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D009570:Nitriles; D009842:Oligopeptides; C113580:U 0126; C433608:verbenachalcone; D020932:Nerve Growth Factor; D048049:Extracellular Signal-Regulated MAP Kinases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; C505410:Casp3 protein, rat; C505524:Casp7 protein, mouse; D053148:Caspase 3; D053179:Caspase 7