The Anti-Breast Cancer Stem Cell Potency of Copper(I)-Non-Steroidal Anti-Inflammatory Drug Complexes

by Selleckchem | Nov 10 2023

Cancer stem cells (CSCs) are thought to be partly responsible for metastasis and cancer relapse. Currently, there are no effective therapeutic options that can remove CSCs at clinically safe doses. Here, we report the synthesis, characterisation, and anti-breast CSC properties of a series of copper(I) complexes, comprising of non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine ligands (1-3). The copper(I) complexes are able to reduce the viability of breast CSCs grown in two- and three-dimensional cultures at micromolar concentrations. The potency of the copper(I) complexes towards breast CSCs was similar to salinomycin (an established anti-breast CSC agent) and cisplatin (a clinically used metallopharmaceutical). Cell-based studies showed that the copper(I) complexes are readily, and similarly, internalised by breast CSCs. The copper(I) complexes significantly increase the intracellular reactive oxygen species (ROS) levels in breast CSCs, and their ROS generation profile with respect to time is dependent on the NSAID component present. The generation of intracellular ROS by the copper(I) complexes could be part of the underlying mechanism by which they evoke breast CSC death. As far as we are aware, this is the first study to explore the anti-breast CSC properties of copper(I) complexes.

Comments:

The research you've described sounds promising in the context of targeting cancer stem cells (CSCs), which are believed to play a crucial role in cancer metastasis and relapse. Here's a breakdown of the key points in your description:

**1. Background:**
- Cancer stem cells (CSCs) are implicated in metastasis and cancer relapse.
- Current therapeutic options are ineffective at eliminating CSCs at safe doses.

**2. Research Focus:**
- A series of copper(I) complexes were synthesized, characterized, and tested for their properties against breast CSCs.
- These copper(I) complexes consist of non-steroidal anti-inflammatory drugs (NSAIDs) and triphenylphosphine ligands.

**3. Results:**
- The copper(I) complexes reduced the viability of breast CSCs in both two- and three-dimensional cell culture models at micromolar concentrations.
- The potency of these copper(I) complexes was similar to that of salinomycin (a known anti-breast CSC agent) and cisplatin (a clinically used metallopharmaceutical).

**4. Mechanism:**
   - The copper(I) complexes were readily internalized by breast CSCs.
   - These complexes increased intracellular levels of reactive oxygen species (ROS) in breast CSCs, with the specific ROS generation profile depending on the NSAID component present.
   - The generation of intracellular ROS by these copper(I) complexes might be a part of the mechanism by which they induce death in breast CSCs.

**5. Significance:**
- This study appears to be the first to explore the potential of copper(I) complexes as agents targeting breast CSCs.

In summary, this research suggests that these copper(I) complexes, which combine NSAIDs and triphenylphosphine ligands, have anti-breast CSC properties that make them effective in reducing the viability of breast CSCs. They seem to operate through mechanisms involving intracellular ROS generation. This is a promising development in the field of cancer research, as it could potentially lead to the development of new therapeutic options for targeting CSCs in breast cancer. However, further studies and clinical trials would be needed to assess their safety and efficacy in humans.