Necroptosis-inducing rhenium(V) oxo complexes

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

doi:10.1021/ja511978y

Necroptosis-inducing rhenium(V) oxo complexes

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^*

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

82 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2967-2974
Number of pages	8
Journal	Journal of the American Chemical Society
Volume	137
Issue number	8
Early online date	20 Feb 2015
DOIs	https://doi.org/10.1021/ja511978y
Publication status	Published - 4 Mar 2015

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title = "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.",

author = "Kogularamanan Suntharalingam and Awuah, {Samuel G.} and Bruno, {Peter M.} and Johnstone, {Timothy C.} and Fang Wang and Wei Lin and Zheng, {Yao Rong} and Page, {Julia E.} and Hemann, {Michael T.} and Lippard, {Stephen J.}",

year = "2015",

month = mar,

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doi = "10.1021/ja511978y",

language = "English",

volume = "137",

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journal = "Journal of the American Chemical Society",

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T1 - Necroptosis-inducing rhenium(V) oxo complexes

AU - Suntharalingam, Kogularamanan

AU - Awuah, Samuel G.

AU - Bruno, Peter M.

AU - Johnstone, Timothy C.

AU - Wang, Fang

AU - Lin, Wei

AU - Zheng, Yao Rong

AU - Page, Julia E.

AU - Hemann, Michael T.

AU - Lippard, Stephen J.

PY - 2015/3/4

Y1 - 2015/3/4

N2 - 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.

AB - 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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DO - 10.1021/ja511978y

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SP - 2967

EP - 2974

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 8

ER -

Necroptosis-inducing rhenium(V) oxo complexes

Abstract

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