The secoiridoid oleuropein is a non-flavonoid polyphenol, found in the fruit, leaves and food derivatives from Olea europea.Like other polyphenols it shows a very low toxicity towards healthy tissues and a protective action against cancer or neurodegeneration, but its mechanism of action is not yet understood.In the present report we have usedoptical and ESR spectroscopy as well as molecular modelling todemonstrate thatoleuropein forms a complex with thetransition metal copper; the dysmetabolism of this metal is suspected to be involved in both cancer and neurodegeneration. Experiments carried out with the aglycon derivative of oleuropein, produced by β-glycosidase treatment of oleuropein glycoside, showed that also the aglycon forms copper-complexes, but with different spectroscopic features than the glycosidic form.Molecular modelling analysis confirmed that two oleuropein molecules (glycosidic or aglycon forms) can easily coordinate one copper ion.The relationship between oleuropein and copper was investigated in SH-SY5Y human neuroblastoma cells.When cells were depleted of copper by treatment with the copper chelator triethylenetetramine (Trien),that binds copper with higher affinity than oleuropein, oleuropein was less toxic than to copper-adequate cells.Conversely, incubation of SH-SY5Y cells with exogenous copper sulphate increased cell susceptibility to oleuropein. FurthermoreSH-SY5Y cells differentiated by retinoic acid pre-treatment showed a lower level of copper,and weremore resistant to oleuropein treatment. The oleuropein aglycon was not toxic towards SH-SY5Y cells. In conclusion, the copper-oleuropeincomplex may be involved in the toxicity of oleuropein towardstumour cells, depending on their copper level.

Capo, C.r., Pedersen, J.z., Falconi, M., Rossi, L. (2017). Oleuropein shows copper complexing properties and noxious effect on cultured SH-SY5Y neuroblastoma cells depending on cell copper content. JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, 44, 225-232 [10.1016/j.jtemb.2017.08.002].

Oleuropein shows copper complexing properties and noxious effect on cultured SH-SY5Y neuroblastoma cells depending on cell copper content

CAPO, CONCETTA ROSA;PEDERSEN, JENS ZACHO;FALCONI, MATTIA;ROSSI, LUISA
2017-12-01

Abstract

The secoiridoid oleuropein is a non-flavonoid polyphenol, found in the fruit, leaves and food derivatives from Olea europea.Like other polyphenols it shows a very low toxicity towards healthy tissues and a protective action against cancer or neurodegeneration, but its mechanism of action is not yet understood.In the present report we have usedoptical and ESR spectroscopy as well as molecular modelling todemonstrate thatoleuropein forms a complex with thetransition metal copper; the dysmetabolism of this metal is suspected to be involved in both cancer and neurodegeneration. Experiments carried out with the aglycon derivative of oleuropein, produced by β-glycosidase treatment of oleuropein glycoside, showed that also the aglycon forms copper-complexes, but with different spectroscopic features than the glycosidic form.Molecular modelling analysis confirmed that two oleuropein molecules (glycosidic or aglycon forms) can easily coordinate one copper ion.The relationship between oleuropein and copper was investigated in SH-SY5Y human neuroblastoma cells.When cells were depleted of copper by treatment with the copper chelator triethylenetetramine (Trien),that binds copper with higher affinity than oleuropein, oleuropein was less toxic than to copper-adequate cells.Conversely, incubation of SH-SY5Y cells with exogenous copper sulphate increased cell susceptibility to oleuropein. FurthermoreSH-SY5Y cells differentiated by retinoic acid pre-treatment showed a lower level of copper,and weremore resistant to oleuropein treatment. The oleuropein aglycon was not toxic towards SH-SY5Y cells. In conclusion, the copper-oleuropeincomplex may be involved in the toxicity of oleuropein towardstumour cells, depending on their copper level.
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Rilevanza internazionale
Articolo
Esperti anonimi
Settore BIO/10
English
Con Impact Factor ISI
oleuropein, copper, SH-SY5Y, cancer, neurodegeneration
http://www.sciencedirect.com/science/article/pii/S0946672X16303546?via=ihub
Capo, C.r., Pedersen, J.z., Falconi, M., Rossi, L. (2017). Oleuropein shows copper complexing properties and noxious effect on cultured SH-SY5Y neuroblastoma cells depending on cell copper content. JOURNAL OF TRACE ELEMENTS IN MEDICINE AND BIOLOGY, 44, 225-232 [10.1016/j.jtemb.2017.08.002].
Capo, Cr; Pedersen, Jz; Falconi, M; Rossi, L
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2108/187545
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