title: Cadmium influences  the 5-Fluorouracil cytotoxic effects on breast cancer cells.
abstract: The aim of the research was to evaluate a heavy metal, Cadmium (Cd), which was used to produce alterations in human breast cancer cell line MCF-7. Moreover, we analyzed both immunohistochemical and ultrastructural alterations induced by the antineoplastic drug, 5-Fluorouracil (5-FU), after exposure to different concentrations of Cadmium. Also, we compared the effects of these compounds on actin and tubulin cytoskeleton proteins. Under ultramicroscopic observation, control cells looked polymorphous with filopodia. In cells already treated with small concentrations of Cd, after brief times of incubation, we observed an intense metabolic activity with larger, clearer, and elongated mitochondria characterized by thin and numerous dilated cristae. 5-FU-treated cells showed cytotoxicity signs with presence of pore-like alterations in the cell membrane and evident degeneration of cytoplasm and cell nuclei. The addition of 5-FU (1.5 μM) to the cells treated with Cd (5 μM-20 μM) did not induce significant ultrastructural changes in comparison with cells treated only with Cd. In Cd+5FU-treated cells mitochondria with globular aspect and regular cristae indicated the active metabolic state. In cells treated only with Cd we observed alterations in actin distribution, while tubulin branched out throughout the cytoplasm. With the association of Cd+5FU, we observed less morphological alterations in both tubulin and actin cytoskeleton proteins. Although the mechanism remains unknown at present, our findings suggest that Cd prevents the cytotoxic effect of 5-FU on breast cancer cells. These preliminary results could have an important clinical application in patients with breast cancer.
authors.affiliation: Department of Biomedical Sciences, University of Sassari, Italy.
authors.forename: Y
authors.initials: Y
authors.lastname: Asara
authors.forename: J A
authors.initials: JA
authors.lastname: Marchal
authors.forename: P
authors.initials: P
authors.lastname: Bandiera
authors.forename: V
authors.initials: V
authors.lastname: Mazzarello
authors.forename: L G
authors.initials: LG
authors.lastname: Delogu
authors.forename: M A
authors.initials: MA
authors.lastname: Sotgiu
authors.forename: A
authors.initials: A
authors.lastname: Montella
authors.forename: R
authors.initials: R
authors.lastname: Madeddu
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000648:ultrastructure*; D002104:Cadmium / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D005260:Female; D005472:Fluorouracil / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure
chemical_list: D000964:Antimetabolites, Antineoplastic; D002104:Cadmium; D005472:Fluorouracil