Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting and cell death pathways

Kogularamanan Suntharalingam; Timothy C. Johnstone; Peter M. Bruno; Wei Lin; Michael T. Hemann; Stephen J. Lippard

doi:10.1021/ja4075375

Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting and cell death pathways

Kogularamanan Suntharalingam, Timothy C. Johnstone, Peter M. Bruno, Wei Lin, Michael T. Hemann, Stephen J. Lippard^*

^*Corresponding author for this work

Chemistry

Massachusetts Institute of Technology

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

88 Citations (Scopus)

Abstract

The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N^N)Cl₃ (N^N = 2,2′-bipyridine 1, 1,10-phenanthroline 2, 3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, 4 evokes endoplasmic reticulum (ER) stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, 4 is the first osmium compound to induce ER stress in cancer cells.

Original language	English
Pages (from-to)	14060-14063
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	135
Issue number	38
DOIs	https://doi.org/10.1021/ja4075375
Publication status	Published - 25 Sept 2013

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10.1021/ja4075375

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@article{7ceabe34eca749c18799623d3a0f1002,

title = "Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting and cell death pathways",

abstract = "The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N^N)Cl3 (N^N = 2,2′-bipyridine 1, 1,10-phenanthroline 2, 3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, 4 evokes endoplasmic reticulum (ER) stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, 4 is the first osmium compound to induce ER stress in cancer cells.",

author = "Kogularamanan Suntharalingam and Johnstone, {Timothy C.} and Bruno, {Peter M.} and Wei Lin and Hemann, {Michael T.} and Lippard, {Stephen J.}",

year = "2013",

month = sep,

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doi = "10.1021/ja4075375",

language = "English",

volume = "135",

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journal = "Journal of the American Chemical Society",

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T1 - Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting and cell death pathways

AU - Suntharalingam, Kogularamanan

AU - Johnstone, Timothy C.

AU - Bruno, Peter M.

AU - Lin, Wei

AU - Hemann, Michael T.

AU - Lippard, Stephen J.

PY - 2013/9/25

Y1 - 2013/9/25

N2 - The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N^N)Cl3 (N^N = 2,2′-bipyridine 1, 1,10-phenanthroline 2, 3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, 4 evokes endoplasmic reticulum (ER) stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, 4 is the first osmium compound to induce ER stress in cancer cells.

AB - The cellular response evoked by antiproliferating osmium(VI) nitrido compounds of general formula OsN(N^N)Cl3 (N^N = 2,2′-bipyridine 1, 1,10-phenanthroline 2, 3,4,7,8-tetramethyl-1,10-phenanthroline 3, or 4,7-diphenyl-1,10-phenanthroline 4) can be tuned by subtle ligand modifications. Complex 2 induces DNA damage, resulting in activation of the p53 pathway, cell cycle arrest at the G2/M phase, and caspase-dependent apoptotic cell death. In contrast, 4 evokes endoplasmic reticulum (ER) stress leading to the upregulation of proteins of the unfolded protein response pathway, increase in ER size, and p53-independent apoptotic cell death. To the best of our knowledge, 4 is the first osmium compound to induce ER stress in cancer cells.

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EP - 14063

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 38

ER -

Bidentate ligands on osmium(VI) nitrido complexes control intracellular targeting and cell death pathways

Abstract

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