Caffeic acid phenethyl ester protects PC12 cells from cisplatin-induced neurotoxicity. - GreenMedInfo Summary
Caffeic Acid Phenethyl Ester (CAPE) Protects PC12 Cells from Cisplatin-Induced Neurotoxicity by Activating the NGF-Signaling Pathway.
Neurotox Res. 2017 Dec 19. Epub 2017 Dec 19. PMID: 29260495
Rafaela Scalco Ferreira
Cisplatin is a highly effective chemotherapeutic drug that is toxic to the peripheral nervous system. Findings suggest that axons are early targets of the neurotoxicity of cisplatin. Although many compounds have been reported as neuroprotective, there is no effective treatment against the neurotoxicity of cisplatin. Caffeic acid phenethyl ester (CAPE) is a propolis component with neuroprotective potential mainly attributed to antioxidant and anti-inflammatory mechanisms. We have recently demonstrated the neurotrophic potential of CAPE in a cellular model of neurotoxicity related to Parkinson's disease. Now, we have assessed the neurotrophic and neuroprotective effects of CAPE against cisplatin-induced neurotoxicity in PC12 cells. CAPE (10 μM) attenuated the inhibition of neuritogenesis and the downregulation of markers of neuroplasticity (GAP-43, synapsin I, synaptophysin, and 200-kD neurofilament) induced by cisplatin (5 μM). This concentration of cisplatin does not affect cell viability, and it was used in order to assess theearly neurotoxic events triggered by cisplatin. When a lethal dose of cisplatin was used (IC50 = 32 μM), CAPE (10 μM) increased cell viability. The neurotrophic effect of CAPE is not dependent on NGF nor is it additive to the effect of NGF, but it might involve the activation of the NGF-high-affinity receptors (trkA). The involvement of other neurotrophin receptors such as trkB and trkC is unlikely. This is the first study to demonstrate the protective potential of CAPE against the neurotoxicity of cisplatin and to suggest the involvement of trkA receptors in the neuroprotective mechanism of CAPE. Based on these findings, the beneficial effect of CAPE on cisplatin-induced peripheral neuropathy should be further investigated.