Targeting mitochondrial DNA with a platinum-based anticancer agent

Simon P. Wisnovsky; Justin J. Wilson; Robert J. Radford; Mark P. Pereira; Maria R. Chan; Rebecca R. Laposa; Stephen J. Lippard; Shana O. Kelley

doi:10.1016/j.chembiol.2013.08.010

Targeting mitochondrial DNA with a platinum-based anticancer agent

Simon P. Wisnovsky, Justin J. Wilson, Robert J. Radford, Mark P. Pereira, Maria R. Chan, Rebecca R. Laposa, Stephen J. Lippard^*, Shana O. Kelley

^*Corresponding author for this work

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

168 Scopus citations

Abstract

An analog of the anticancer drug cisplatin (mtPt) was delivered to mitochondria of human cells using a peptide specifically targeting this organelle. mtPt induces apoptosis without damaging nuclear DNA, indicating that mtDNA damage is sufficient to mediate the activity of a platinum-based chemotherapeutic. This study demonstrates the specific delivery of a platinum drug to mitochondria and investigates the effects of directing this agent outside the nucleus.

Original language	English (US)
Pages (from-to)	1323-1328
Number of pages	6
Journal	Chemistry and Biology
Volume	20
Issue number	11
DOIs	https://doi.org/10.1016/j.chembiol.2013.08.010
State	Published - Nov 21 2013
Externally published	Yes

ASJC Scopus subject areas

Drug Discovery
Molecular Medicine
Molecular Biology
Biochemistry
Clinical Biochemistry
Pharmacology

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10.1016/j.chembiol.2013.08.010

Cite this

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title = "Targeting mitochondrial DNA with a platinum-based anticancer agent",

abstract = "An analog of the anticancer drug cisplatin (mtPt) was delivered to mitochondria of human cells using a peptide specifically targeting this organelle. mtPt induces apoptosis without damaging nuclear DNA, indicating that mtDNA damage is sufficient to mediate the activity of a platinum-based chemotherapeutic. This study demonstrates the specific delivery of a platinum drug to mitochondria and investigates the effects of directing this agent outside the nucleus.",

author = "Wisnovsky, {Simon P.} and Wilson, {Justin J.} and Radford, {Robert J.} and Pereira, {Mark P.} and Chan, {Maria R.} and Laposa, {Rebecca R.} and Lippard, {Stephen J.} and Kelley, {Shana O.}",

note = "Funding Information: Work in the lab of S.J.L. was supported by the National Cancer Institute under grant CA034992. J.J.W. is supported by a David H. Koch Graduate Fellowship. Work in the lab of S.O.K. was supported by the Canadian Institute of Health. Dr. Tomas Prolla (University of Wisconsin-Madison) provided PolgD257A mice from which mouse embryonic fibroblasts were generated. S.J.L. declares a financial interest in Blend Therapeutics. ",

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doi = "10.1016/j.chembiol.2013.08.010",

language = "English (US)",

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AU - Wisnovsky, Simon P.

AU - Wilson, Justin J.

AU - Radford, Robert J.

AU - Pereira, Mark P.

AU - Chan, Maria R.

AU - Laposa, Rebecca R.

AU - Lippard, Stephen J.

AU - Kelley, Shana O.

N1 - Funding Information: Work in the lab of S.J.L. was supported by the National Cancer Institute under grant CA034992. J.J.W. is supported by a David H. Koch Graduate Fellowship. Work in the lab of S.O.K. was supported by the Canadian Institute of Health. Dr. Tomas Prolla (University of Wisconsin-Madison) provided PolgD257A mice from which mouse embryonic fibroblasts were generated. S.J.L. declares a financial interest in Blend Therapeutics.

PY - 2013/11/21

Y1 - 2013/11/21

N2 - An analog of the anticancer drug cisplatin (mtPt) was delivered to mitochondria of human cells using a peptide specifically targeting this organelle. mtPt induces apoptosis without damaging nuclear DNA, indicating that mtDNA damage is sufficient to mediate the activity of a platinum-based chemotherapeutic. This study demonstrates the specific delivery of a platinum drug to mitochondria and investigates the effects of directing this agent outside the nucleus.

AB - An analog of the anticancer drug cisplatin (mtPt) was delivered to mitochondria of human cells using a peptide specifically targeting this organelle. mtPt induces apoptosis without damaging nuclear DNA, indicating that mtDNA damage is sufficient to mediate the activity of a platinum-based chemotherapeutic. This study demonstrates the specific delivery of a platinum drug to mitochondria and investigates the effects of directing this agent outside the nucleus.

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Targeting mitochondrial DNA with a platinum-based anticancer agent

Abstract

ASJC Scopus subject areas

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