Abstract
Four copper(II) complexes, 1-4 containing regioisomeric vanillin Schiff base derivatives ((E)-5/4/3/2-methoxy-2-(((2-(methylthio)ethyl)imino)methyl)phenol) and the nonsteroidal anti-inflammatory drug (NSAID), naproxen, were synthesised and characterised. All complexes effectively cleave DNA in cell-free systems, with 4 displaying the highest nuclease activity. DNA binding studies suggest that 4 binds to DNA via the grooves prior to inducing oxidative DNA cleavage. Three of the complexes (1, 3, and 4) indiscriminately kill cancer stem cell (CSC)-enriched cells (HMLER-shEcad) and bulk cancer cells (HMLER) at micromolar concentrations. The most effective complex, 4 also reduced the formation and size of mammospheres to a similar extent as salinomycin, a well-established CSC-potent agent. Mechanistic studies show that 4 is readily taken up by CSCs, elevates intracellular reactive oxygen species (ROS) levels, causes DNA damage, and induces caspase-dependent apoptosis. Furthermore, 4 inhibits cyclooxygenase-2 (COX-2) expression and causes COX-2-dependent CSC death. The advantage of 4 over bulk cancer cell- or CSC-selective agents is that it has the potential to remove whole tumor populations (bulk cancer cells and CSCs) with a single dose.
| Original language | English |
|---|---|
| Pages (from-to) | 11366-11374 |
| Number of pages | 9 |
| Journal | CHEMISTRY |
| Volume | 23 |
| Issue number | 47 |
| Early online date | 28 Jun 2017 |
| DOIs | |
| Publication status | Published - 3 Aug 2017 |
Access to Document
- Cancer Stem Cell and_LU_Publishedonline28June2017_GREEN AAM
This is the peer reviewed version of the following article: Lu, C. et al., 'Cancer Stem Cell and Bulk Cancer Cell Active Copper(II) Complexes with Vanillin Schiff Base Derivatives and Naproxen', Chemistry: A European Journal, (Wiley, 2017), which has been published in final form at http://dx.doi.org/10.1002/chem.201701939. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.