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Necroptosis-Inducing Rhenium(V) Oxo Complexes

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.; ... Show more Show less
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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.
Date issued
2015-02
URI
http://hdl.handle.net/1721.1/110417
Department
David H. Koch Institute for Integrative Cancer Research at MIT; Massachusetts Institute of Technology. Department of Chemistry
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
ISSN
0002-7863
1520-5126

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