Necroptosis-inducing rhenium(V) oxo complexes.

Abstract

Rhenium(V) oxo complexes of general formula [ReO(OMe)(N^N)Cl2], where N^N = 4,7-diphenyl-1,10-phenanthroline, 1, or 3,4,7,8-tetramethyl-1,10-phenanthroline, 2, effectively kill cancer cells by triggering necroptosis, a non-apoptotic form of cell death. Both complexes evoke necrosome (RIP1-RIP3)-dependent intracellular reactive oxygen species (ROS) production and propidium iodide uptake. The complexes also induce mitochondrial membrane potential depletion, a possible downstream effect of ROS production. Apparently, 1 and 2 are the first rhenium complexes to evoke cellular events consistent with programmed necrosis in cancer cells. Furthermore, 1 and 2 display low acute toxicity in C57BL/6 mice and reasonable stability in fresh human blood.

• Authors: Kogularamanan Suntharalingam, Samuel G Awuah, Peter M Bruno, Timothy C Johnstone, Fang Wang, Wei Lin, Yao-Rong Zheng, Julia E Page, Michael T Hemann, Stephen J Lippard
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 137 Issue 8 Pg. 2967-74 (Mar 04 2015) ISSN: 1520-5126 [Electronic] United States
• PMID: 25698398 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Organometallic Compounds
• Phenanthrolines
• Receptor, PAR-1
• Tumor Suppressor Protein p53
• Rhenium
• 1,10-phenanthroline

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology, toxicity)
• Apoptosis (drug effects)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Drug Stability
• Humans
• Mice
• Models, Molecular
• Molecular Conformation
• Necrosis (chemically induced)
• Organometallic Compounds (chemical synthesis, chemistry, pharmacology, toxicity)
• Phenanthrolines (chemistry)
• Receptor, PAR-1 (metabolism)
• Rhenium (chemistry)
• Tumor Suppressor Protein p53 (metabolism)