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.

The APE1 redox inhibitor E3330 reduces collective cell migration of human breast cancer cells and decreases chemoinvasion and colony formation when combined with docetaxel

“…The in vitro wound‐healing assay was performed using a previously described protocol . MDA‐MB‐231 cells were cultured in 24‐well plates at a seeding density of 2.75 × 10 5 cells per well.…”

“…The chemotactic migration and chemoinvasion of MDA‐MB‐231 cells were evaluated by adopting a protocol already described . The chemotaxis was assessed in 24‐well plates by seeding 1 × 10 5 cells in serum‐free medium on the top of a transwell insert with transparent PET membranes containing 8‐μm pores (BD Biosciences, USA).…”

Anti-Migratory and Pro-Apoptotic Properties of Parvifloron D on Triple-Negative Breast Cancer Cells

“…Cells resuspended in the FBS-free medium were seeded on the top of the insert, and complete medium was placed in the lower chamber of the culture well. A ParvD concentration of 1 µM was added in both chambers and cells were incubated for 24 h. The evaluation of the chemotactic migration was performed following a previously described protocol [28]. The results were expressed as percentages of non-treated control cultures.…”

“…To evaluate cell adhesion, MDA-MB-231 cells were cultured in 24-well plates for 24 h, to achieve a confluence of approximately 30%. Cells were then incubated with several ParvD concentrations (0, 1 and 2 µM) for a period of 24 h. The EDTA-induced cell detachment assay was performed following previously described protocols [28,29].…”

Genome-wide analysis of transcription and photosynthesis inhibition in the harmful dinoflagellate Prorocentrum minimum in response to the biocide copper sulfate

“…Cell motility showed the highest differentially expressed percentage (65%) in KEGG pathways analysis, indicating that Prorocentrum minimum cell motility should be affected by CuSO 4 . Excess copper inhibited the motility of the microalgae Isochrysis galbana and Tetraselmis chui (Liu et al, 2011); the Cu 2+ complex Cu[15]pyN 5 also caused reduced cell motility in breast cancer cells (Fernandes et al, 2015).…”