Necroptosis-Inducing Rhenium(V) Oxo Complexes
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)-depe...
Main Authors: | , , , , , , , , , |
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Other Authors: | |
Format: | Article |
Language: | en_US |
Published: |
American Chemical Society (ACS)
2017
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Online Access: | http://hdl.handle.net/1721.1/110417 https://orcid.org/0000-0002-6958-3991 https://orcid.org/0000-0003-3383-0118 https://orcid.org/0000-0002-9192-6858 https://orcid.org/0000-0002-2693-4982 |
Summary: | 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. |
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