Necroptosis-Inducing Rhenium(V) Oxo Complexes
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Lippard_Necroptosis-inducing.pdf
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Author(s)
Suntharalingam, Kogularamanan
Awuah, Samuel
Bruno, Peter Michael
Johnstone, Timothy
Wang, Fang
Lin, Wei
Zheng, Yaorong
Page, Julia E.
Hemann, Michael
Lippard, Stephen J.
Date Issued
February 2015
Journal
Journal of the American Chemical Society
Publisher
American Chemical Society (ACS)
Citation
Suntharalingam, Kogularamanan; Awuah, Samuel G.; Bruno, Peter M.; Johnstone, Timothy C.; Wang, Fang; Lin, Wei; Zheng, Yao-Rong; Page, Julia E.; Hemann, Michael T. and Lippard, Stephen J. “Necroptosis-Inducing Rhenium(V) Oxo Complexes.” Journal of the American Chemical Society 137, 8 (March 2015): 2967–2974 © 2015 American Chemical Society
Version
Author's final manuscript
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.
MIT Department
Massachusetts Institute of Technology. Department of Chemistry
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.1021/ja511978y
