TY - JOUR
T1 - Polypyridyl zinc(II)-Indomethacin complexes with potent anti-breast cancer stem cell activity
AU - Rundstadler, Tiffany K.
AU - Eskandari, Arvin
AU - Norman, Sarah M.
AU - Suntharalingam, Kogularamanan
PY - 2018/9/4
Y1 - 2018/9/4
N2 - 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.
AB - 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.
KW - Bioinorganic chemistry
KW - Metallopharmaceuticals
KW - Nonsteroidal anti-inflammatory drug
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=85052895206&partnerID=8YFLogxK
U2 - 10.3390/molecules23092253
DO - 10.3390/molecules23092253
M3 - Article
AN - SCOPUS:85052895206
SN - 1420-3049
VL - 23
JO - Molecules
JF - Molecules
IS - 9
M1 - 2253
ER -
