Unlike reactivity of mono- and binuclear imine-copper(II) complexes toward melanoma cells via a tyrosinase-dependent mechanism.

Unlike reactivity of mono- and binuclear imine-copper(II) complexes toward melanoma cells via a tyrosinase-dependent mechanism.

Publication date: Aug 08, 2019

The cytotoxicity of a dinuclear imine-copper (II) complex 2, and its analogous mononuclear complex 1, toward different melanoma cells, particularly human SKMEL-05 and SKMEL-147, was investigated. Complex 2, a tyrosinase mimic, showed much higher activity in comparison to complex 1, and its reactivity was verified to be remarkably activated by UVB-light, while the mononuclear compound showed a small or negligible effect. Further, a significant dependence on the melanin content in the tumor cells, both from intrinsic pigmentation or stimulated by irradiation, was observed in the case of complex 2. Similar tests with keratinocytes and melanocytes indicated a much lower sensitivity to both copper (II) complexes, even after exposition to UV light. Clonogenic assays attested that the fractions of melanoma cells survival were much lower under treatment with complex 2 compared to complex 1, both with or without previous irradiation of the cells. The process also involves generation of reactive oxygen species (ROS), as verified by EPR spectroscopy, and by using fluorescence indicators. Autophagic assays indicated a remarkable formation of cytoplasmic vacuoles in melanomas treated with complex 2, while this effect was not observed in similar treatment with complex 1. Monitoring of specific protein LC3 corroborated the simultaneous occurrence of autophagy. A balance interplay between different modes of cell death, apoptosis and autophagy, occurs when melanomas were treated with the dinuclear complex 2, in contrast to the mononuclear complex 1. These results pointed out to different mechanisms of action of such complexes, depending on its nuclearity.

Nunes, C.J., Otake, A.H., Bustos, S.O., Fazzi, R.B., Chammas, R., and Da Costa Ferreira, A.M. Unlike reactivity of mono- and binuclear imine-copper(II) complexes toward melanoma cells via a tyrosinase-dependent mechanism. 23716. 2019 Chem Biol Interact.

Concepts Keywords
Apoptosis Branches of biology
Autophagy Medical specialties
Copper Immunology
Cytotoxicity Biochemistry
EPR Spectroscopy Melanoma
Exposition Cancer
Fluorescence RTT
Imine Melanocyte
Interplay Tyrosinase
Keratinocytes Autophagy
Melanin Assay
Melanocytes Apoptosis
Melanoma Spectroscopy
Melanomas
Mono
Oxygen
ROS
Tumor
Tyrosinase
UVB Light
Vacuoles

Semantics

Type Source Name
pathway BSID Melanogenesis
pathway BSID Apoptosis
drug DRUGBANK Isoxaflutole
gene UNIPROT ROS1
disease MESH tumor
gene UNIPROT TNFSF14
gene UNIPROT TYR
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
drug DRUGBANK Copper

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