Polypyridyl Zinc(II)-Indomethacin Complexes with Potent Anti-Breast Cancer Stem Cell Activity

• Main Authors: Tiffany K. Rundstadler, Arvin Eskandari, Sarah M. Norman, Kogularamanan Suntharalingam
• Format: Article
• Language: English
• Published: MDPI AG 2018-09-01
• Series: Molecules
• Subjects: metallopharmaceuticals; bioinorganic chemistry; zinc; nonsteroidal anti-inflammatory drug
• Online Access: http://www.mdpi.com/1420-3049/23/9/2253

Cancer stem cells (CSCs) are thought of as a clinically pertinent subpopulation of tumors, partly responsible for cancer relapse and metastasis. Research programs aimed at discovering anti-CSC agents have largely focused on biologics and purely organic molecules. Recently, we showed that a family of redox-active copper(II) complexes with phenanthroline-based ligands and nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin, are capable of potently and selectively killing breast CSCs. Herein we present analogous redox-inactive, zinc(II)-phenanthroline-indomethacin complexes with the ability to kill breast CSCs and bulk breast cancer cells with equal potency (in the submicro- or micromolar range). A single dose of the zinc(II) complexes could theoretically be administered to eliminate whole tumor populations. Excitingly, some of the zinc(II) complexes decrease the growth and viability of mammospheres to a comparable or higher degree than salinomycin, a compound known to effectively kill breast CSCs. As far as we are aware this is the first report to examine the anti-breast CSC activity of zinc(II)-containing compounds.