title: Role of the Copper(II) Complex Cu[15]pyN5 in Intracellular ROS and Breast Cancer Cell Motility and Invasion.
abstract: Multiple mechanisms related to metastases undergo redox regulation. Cu[15]pyN5 is a redox-active copper(II) complex previously studied as a chemotherapy sensitizer in mammary cells. The effects of a cotreatment with Cu[15]pyN5 and doxorubicin (dox) were evaluated in two human breast cancer cell lines: MCF7 (low aggressiveness) and MDA-MB-231 (highly aggressive). Cu[15]pyN5 decreased MCF7-directed cell migration. In addition, a cotreatment with dox and Cu[15]pyN5 reduced the proteolytic invasion of MDA-MB-231 cells. Cell detachment was not affected by exposure to these agents. Cu[15]pyN5 and dox significantly increased intracellular ROS in both cell lines. This increase could be at least partially due to H2 O2 accumulation. The combination of Cu[15]pyN5 with dox may be beneficial in breast cancer treatment as it could help reduce cancer cell migration and invasion. Moreover, the ligand [15]pyN5 has a high affinity for copper(II) and displays potential anti-angiogenic properties. Overall, we present a potential drug that might arrest the progression of breast cancer by different and complementary mechanisms.
authors.affiliation: CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, Lisboa, 1749-024, Portugal.
authors.forename: Ana S
authors.identifier: http://orcid.org/0000-0001-6350-0641
authors.initials: AS
authors.lastname: Fernandes
authors.affiliation: CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, Lisboa, 1749-024, Portugal.|Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: Ana
authors.initials: A
authors.lastname: Flórido
authors.affiliation: CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, Lisboa, 1749-024, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Saraiva
authors.affiliation: CBIOS, Universidade Lusófona Research Center for Biosciences & Health Technologies, Campo Grande 376, Lisboa, 1749-024, Portugal.
authors.forename: Sara
authors.initials: S
authors.lastname: Cerqueira
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: Sérgio
authors.initials: S
authors.lastname: Ramalhete
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: Madalena
authors.initials: M
authors.lastname: Cipriano
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: Maria Fátima
authors.initials: MF
authors.lastname: Cabral
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: Joana P
authors.initials: JP
authors.lastname: Miranda
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: Matilde
authors.initials: M
authors.lastname: Castro
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: Judite
authors.initials: J
authors.lastname: Costa
authors.affiliation: Research Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Av. Professor Gama Pinto, 1649-003, Lisboa, Portugal.
authors.forename: Nuno G
authors.initials: NG
authors.lastname: Oliveira
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement / Q000187:drug effects*; D003300:Copper / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D017382:Reactive Oxygen Species / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D017382:Reactive Oxygen Species; D003300:Copper; D004317:Doxorubicin
keywords: angiogenesis; breast cancer; cell migration and invasion; doxorubicin; macrocyclic copper(II) complex; redox modulation