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: Ana S Fernandes, Ana Flórido, Nuno Saraiva, Sara Cerqueira, Sérgio Ramalhete, Madalena Cipriano, Maria Fátima Cabral, Joana P Miranda, Matilde Castro, Judite Costa, Nuno G Oliveira
• Journal: Chemical biology & drug design (Chem Biol Drug Des) Vol. 86 Issue 4 Pg. 578-88 (Oct 2015) ISSN: 1747-0285 [Electronic] England
• PMID: 25600158 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2015 John Wiley & Sons A/S.

Chemical References

• Antineoplastic Agents
• Reactive Oxygen Species
• Copper
• Doxorubicin

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Cell Movement (drug effects)
• Copper (chemistry, pharmacology)
• Doxorubicin (chemistry, pharmacology)
• Female
• Humans
• MCF-7 Cells
• Reactive Oxygen Species (metabolism)