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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
Nunes, Cleia Justino [1] ; Otake, Andreia Hanada [2] ; Bustos, Silvina Odete [2] ; Fazzi, Rodrigo Boni [1] ; Chammas, Roger [2] ; Da Costa Ferreira, Ana Maria [1]
Total Authors: 6
Affiliation:
[1] Univ Sao Paulo, Inst Quim, Dept Quim Fundamental, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Fac Med, ICESP, BR-01246000 Sao Paulo, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: Chemico-Biological Interactions; v. 311, SEP 25 2019.
Web of Science Citations: 1
Abstract

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. (AU)

FAPESP's process: 11/50318-1 - Development of compounds with pharmacological or medicinal interest and of systems for their transport, detection and recognition in biological media
Grantee:Ana Maria da Costa Ferreira
Support Opportunities: Research Projects - Thematic Grants
FAPESP's process: 13/07937-8 - Redoxome - Redox Processes in Biomedicine
Grantee:Ohara Augusto
Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC