Anticancer copper complex with nucleus, mitochondrion and cyclooxygenase-2 as multiple targets.

Abstract

Copper complexes are hopeful anticancer drugs due to their multifacet biological properties and high biocompatibility. Inflammatory environment plays an important role in tumor progression and affects the body response to chemotherapeutic agents. A copper(II) complex CuLA with a phenanthroline derivative N-(1,10-phenanthrolin-5-yl)-nonanamide (L) and two aspirin anions (A) as the ligands was synthesized. CuLA effectively induces mitochondrial dysfunction and promotes early-apoptosis in SKOV-3 cells; moreover, it suppresses the expression of cyclooxygenase-2, a key enzyme involved in inflammatory response, in lipopolysaccharide stimulated RAW 264.7 cells. By contrast, the analogue complex CuL without aspirin ligand shows similar influences on cellular redox homeostasis and cell cycle progression but relatively low cytotoxic activity due to its mild effect on mitochondrial function; more importantly, it lacks inhibition to cyclooxygenase-2. The results demonstrate that CuLA inhibits cancer cells through dual pathways involving DNA damage and mitochondrial dysfunction. The introduction of aspirin not only enhances the antitumour efficacy but also reduces the inflammatory threat. Copper complexes with both antitumor and anti-inflammatory activities may represent a new type of multifunctional metal complexes in hope to be developed into novel metallodrugs.

• Authors: Xiangchao Shi, Hongbao Fang, Yan Guo, Hao Yuan, Zijian Guo, Xiaoyong Wang
• Journal: Journal of inorganic biochemistry (J Inorg Biochem) Vol. 190 Pg. 38-44 (01 2019) ISSN: 1873-3344 [Electronic] United States
• PMID: 30352314 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018. Published by Elsevier Inc.

Chemical References

• Antineoplastic Agents
• Coordination Complexes
• Copper
• Cyclooxygenase 2

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Nucleus (chemistry)
• Coordination Complexes (chemistry, pharmacology)
• Copper (chemistry)
• Cyclooxygenase 2 (chemistry, drug effects)
• DNA Damage
• Humans
• Mitochondria (chemistry, drug effects)