title: Cytotoxic effects of cadmium in mammary epithelial cells: protective role of the macrocycle [15]pyN5.
abstract: Human exposure to cadmium (Cd) occurs via different routes, including diet. The increasing amount of data linking Cd with different cellular effects in the mammary gland justifies additional toxicological assessments using human mammary epithelial cells. This work aimed therefore to assess the cytotoxic effects of Cd in MCF10A cells and to characterize the cytoprotective role of the macrocycle [15]pyN(5) in the form of calcium salt. Cadmium chloride revealed to be cytotoxic to MCF10A cells, decreasing cell viability and proliferation in a concentration-dependent manner. Comparable dose-response curves and IC50 values (57-63 μM, 24h treatment) were obtained using the MTT reduction, crystal violet and BrdU assays. In terms of reactive oxygen species formation, only a slight increase in superoxide radical anion was observed at very high Cd concentrations (≥100 μM). Chelation should thus constitute the primary strategy to mitigate the cytotoxic effects induced by Cd in mammary cells. In this context, [15]pyN(5) which presents appropriate chemical and thermodynamic features was studied as a Cd chelator. This macrocycle (25 and 50 μM) significantly reduced or even abolished Cd-induced cytotoxicity. Protective effects were observed in terms of cell viability, cell proliferation and morphological alterations, being the protection mostly attributed to a chelating-based mechanism.
authors.affiliation: Research Institute for Medicines and Pharmaceutical Sciences (iMed.UL), Faculty of Pharmacy, University of Lisbon, Av. Prof. Gama Pinto, 1649-003 Lisbon, Portugal.
authors.forename: Sandrina
authors.initials: S
authors.lastname: Gonçalves
authors.forename: Ana Sofia
authors.initials: AS
authors.lastname: Fernandes
authors.forename: Nuno G
authors.initials: NG
authors.lastname: Oliveira
authors.forename: Joana
authors.initials: J
authors.lastname: Marques
authors.forename: Judite
authors.initials: J
authors.lastname: Costa
authors.forename: M Fátima
authors.initials: MF
authors.lastname: Cabral
authors.forename: Joana
authors.initials: J
authors.lastname: Miranda
authors.forename: Madalena
authors.initials: M
authors.lastname: Cipriano
authors.forename: Patrícia S
authors.initials: PS
authors.lastname: Guerreiro
authors.forename: Matilde
authors.initials: M
authors.lastname: Castro
mesh_terms: D000963:Antimetabolites; D001973:Bromodeoxyuridine; D019256:Cadmium Chloride / Q000633:toxicity*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D004396:Coloring Agents; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects*; D005260:Female; D005470:Fluorometry; D005840:Gentian Violet; D006801:Humans; D047028:Macrocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D042361:Mammary Glands, Human / Q000166:cytology* / Q000187:drug effects; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013816:Thermodynamics; D013844:Thiazoles
chemical_list: C575437:(15)pyN5; D000963:Antimetabolites; D002614:Chelating Agents; D004396:Coloring Agents; D047028:Macrocyclic Compounds; D017382:Reactive Oxygen Species; D013778:Tetrazolium Salts; D013844:Thiazoles; C022616:thiazolyl blue; D001973:Bromodeoxyuridine; D005840:Gentian Violet; D019256:Cadmium Chloride