A breast cancer stem cell-selective, mammospheres-potent osmium(VI) nitrido complex

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

doi:10.1021/ja508808v

A breast cancer stem cell-selective, mammospheres-potent osmium(VI) nitrido complex

Kogularamanan Suntharalingam, Wei Lin, Timothy C. Johnstone, Peter M. Bruno, Yao Rong Zheng, 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 effect of a newly developed osmium(VI) nitrido complex, 1, on breast cancer stem cells (CSCs) is reported. The complex displays selective toxicity for HMLER breast cancer cells enriched with CD44-positive, CSC-like cells over the same cells having reduced CSC character. Remarkably, 1 also reduces the proportion of CSCs within a heterogeneous breast cancer cell population and irreversibly inhibits the formation of free-floating mammospheres to an extent similar to that of salinomycin, a natural product that targets CSCs. Detailed mechanistic studies reveal that in breast cancer cells 1 induces DNA damage and endoplasmic reticulum stress, the latter being responsible for the CSC selectivity. The anti-CSC properties of 1 provide a strong impetus for the development of new metal-based compounds to target CSCs and to treat chemotherapy-resistant and relapsed tumors.

Original language	English
Pages (from-to)	14413-14416
Number of pages	4
Journal	Journal of the American Chemical Society
Volume	136
Issue number	41
Early online date	6 Oct 2014
DOIs	https://doi.org/10.1021/ja508808v
Publication status	Published - 15 Oct 2014

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1021/ja508808v

Cite this

@article{548019c3d77f46358d43898944128e42,

title = "A breast cancer stem cell-selective, mammospheres-potent osmium(VI) nitrido complex",

abstract = "The effect of a newly developed osmium(VI) nitrido complex, 1, on breast cancer stem cells (CSCs) is reported. The complex displays selective toxicity for HMLER breast cancer cells enriched with CD44-positive, CSC-like cells over the same cells having reduced CSC character. Remarkably, 1 also reduces the proportion of CSCs within a heterogeneous breast cancer cell population and irreversibly inhibits the formation of free-floating mammospheres to an extent similar to that of salinomycin, a natural product that targets CSCs. Detailed mechanistic studies reveal that in breast cancer cells 1 induces DNA damage and endoplasmic reticulum stress, the latter being responsible for the CSC selectivity. The anti-CSC properties of 1 provide a strong impetus for the development of new metal-based compounds to target CSCs and to treat chemotherapy-resistant and relapsed tumors.",

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

year = "2014",

month = oct,

day = "15",

doi = "10.1021/ja508808v",

language = "English",

volume = "136",

pages = "14413--14416",

journal = "Journal of the American Chemical Society",

issn = "0002-7863",

publisher = "American Chemical Society",

number = "41",

}

TY - JOUR

T1 - A breast cancer stem cell-selective, mammospheres-potent osmium(VI) nitrido complex

AU - Suntharalingam, Kogularamanan

AU - Lin, Wei

AU - Johnstone, Timothy C.

AU - Bruno, Peter M.

AU - Zheng, Yao Rong

AU - Hemann, Michael T.

AU - Lippard, Stephen J.

PY - 2014/10/15

Y1 - 2014/10/15

N2 - The effect of a newly developed osmium(VI) nitrido complex, 1, on breast cancer stem cells (CSCs) is reported. The complex displays selective toxicity for HMLER breast cancer cells enriched with CD44-positive, CSC-like cells over the same cells having reduced CSC character. Remarkably, 1 also reduces the proportion of CSCs within a heterogeneous breast cancer cell population and irreversibly inhibits the formation of free-floating mammospheres to an extent similar to that of salinomycin, a natural product that targets CSCs. Detailed mechanistic studies reveal that in breast cancer cells 1 induces DNA damage and endoplasmic reticulum stress, the latter being responsible for the CSC selectivity. The anti-CSC properties of 1 provide a strong impetus for the development of new metal-based compounds to target CSCs and to treat chemotherapy-resistant and relapsed tumors.

AB - The effect of a newly developed osmium(VI) nitrido complex, 1, on breast cancer stem cells (CSCs) is reported. The complex displays selective toxicity for HMLER breast cancer cells enriched with CD44-positive, CSC-like cells over the same cells having reduced CSC character. Remarkably, 1 also reduces the proportion of CSCs within a heterogeneous breast cancer cell population and irreversibly inhibits the formation of free-floating mammospheres to an extent similar to that of salinomycin, a natural product that targets CSCs. Detailed mechanistic studies reveal that in breast cancer cells 1 induces DNA damage and endoplasmic reticulum stress, the latter being responsible for the CSC selectivity. The anti-CSC properties of 1 provide a strong impetus for the development of new metal-based compounds to target CSCs and to treat chemotherapy-resistant and relapsed tumors.

UR - http://www.scopus.com/inward/record.url?scp=84908388798&partnerID=8YFLogxK

U2 - 10.1021/ja508808v

DO - 10.1021/ja508808v

M3 - Article

AN - SCOPUS:84908388798

SN - 0002-7863

VL - 136

SP - 14413

EP - 14416

JO - Journal of the American Chemical Society

JF - Journal of the American Chemical Society

IS - 41

ER -

A breast cancer stem cell-selective, mammospheres-potent osmium(VI) nitrido complex

Abstract

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this