Preclinical anti-cancer activity and multiple mechanisms of action of a cationic silver complex bearing N-heterocyclic carbene ligands

• Published in: Cancer letters Vol. 403; pp. 98 - 107
• Main Authors: Allison, Simon J., Sadiq, Maria, Baronou, Efstathia, Cooper, Patricia A., Dunnill, Chris, Georgopoulos, Nikolaos T., Latif, Ayşe, Shepherd, Samantha, Shnyder, Steve D., Stratford, Ian J., Wheelhouse, Richard T., Willans, Charlotte E., Phillips, Roger M.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 10.09.2017; Elsevier Limited
• Subjects: Antigens, Neoplasm - metabolism; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antineoplastic Agents - toxicity; Antineoplastic Combined Chemotherapy Protocols - pharmacology; Apoptosis; Apoptosis - drug effects; Cancer; Cancer therapies; Cell death; Cell Line, Tumor; Cell Survival - drug effects; Cisplatin; Cisplatin - pharmacology; Cytotoxicity; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacology; Deoxyribonucleic acid; DNA; DNA Damage; DNA repair; DNA topoisomerase; DNA Topoisomerases, Type I - metabolism; DNA Topoisomerases, Type II - metabolism; DNA-Binding Proteins - metabolism; Dose-Response Relationship, Drug; Drug Resistance, Neoplasm; Drug Synergism; Flow cytometry; Glycolysis; Glycolysis - drug effects; Glycolytic inhibitor; Gold; Hematology, Oncology and Palliative Medicine; Humans; Imidazoles - chemistry; Imidazoles - pharmacology; Imidazoles - toxicity; Inhibitory Concentration 50; Kinases; Ligands; Neoplasms - drug therapy; Neoplasms - metabolism; Neoplasms - pathology; Organometallic complexes; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Organometallic Compounds - toxicity; Oxidative Stress - drug effects; PARP1 inhibitor; Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors; Poly (ADP-Ribose) Polymerase-1 - metabolism; Poly(ADP-ribose) polymerase; Poly(ADP-ribose) Polymerase Inhibitors - pharmacology; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reductase; Signal Transduction - drug effects; Silver; Silver-N-heterocyclic carbene; Temozolomide; Thioredoxin; Thioredoxin Reductase 1 - antagonists & inhibitors; Thioredoxin Reductase 1 - metabolism; Thioredoxin reductase inhibitor; Topoisomerase I Inhibitors - pharmacology; Topoisomerase II Inhibitors - pharmacology; Topoisomerase inhibitor; Tumors; Thioredoxin reductase inhibitor; Silver-N-heterocyclic carbene; PARP1 inhibitor; Topoisomerase inhibitor; Glycolytic inhibitor; Silver- N-heterocyclic carbene

Organometallic complexes offer the prospect of targeting multiple pathways that are important in cancer biology. Here, the preclinical activity and mechanism(s) of action of a silver-bis(N-heterocyclic carbine) complex (Ag8) were evaluated. Ag8 induced DNA damage via several mechanisms including top...