Metal-based inhibition of poly(ADP-ribose) polymerase-the guardian angel of DNA

Filipa Mendes; Michael Groessl; Alexey A. Nazarov; Yury O. Tsybin; Gianni Sava; Isabel Santos; Paul J. Dyson; Angela Casini

doi:10.1021/jm2000135

Metal-based inhibition of poly(ADP-ribose) polymerase-the guardian angel of DNA

Filipa Mendes, Michael Groessl, Alexey A. Nazarov, Yury O. Tsybin, Gianni Sava, Isabel Santos, Paul J. Dyson, Angela Casini

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

137 Scopus citations

Abstract

The inhibition activity of a series of anticancer metal complexes based on platinum, ruthenium, and gold metal ions was evaluated on the zinc-finger protein PARP-1, either purified or directly on protein extracts from human breast cancer MCF7 cells. Information on the reactivity of the metal complexes with the PARP-1 zinc-finger domain was obtained by high-resolution ESI FT-ICR mass spectrometry. An excellent correlation between PARP-1 inhibition in protein extracts and the ability of the complexes to bind to the zinc-finger motif (in competition with zinc) was established. The results support a model whereby displacement of zinc from the PARP-1 zinc finger by other metal ions leads to decreased PARP-1 activity. In vitro combination studies of cisplatin with NAMI-A and RAPTA-T on different cancer cell lines (MCF7, A2780, and A2780cisR) showed that, in some cases, a synergistic effect is in operation.

Original language	English
Pages (from-to)	2196-2206
Number of pages	11
Journal	Journal of Medicinal Chemistry
Volume	54
Issue number	7
DOIs	https://doi.org/10.1021/jm2000135
State	Published - 14 Apr 2011
Externally published	Yes

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title = "Metal-based inhibition of poly(ADP-ribose) polymerase-the guardian angel of DNA",

abstract = "The inhibition activity of a series of anticancer metal complexes based on platinum, ruthenium, and gold metal ions was evaluated on the zinc-finger protein PARP-1, either purified or directly on protein extracts from human breast cancer MCF7 cells. Information on the reactivity of the metal complexes with the PARP-1 zinc-finger domain was obtained by high-resolution ESI FT-ICR mass spectrometry. An excellent correlation between PARP-1 inhibition in protein extracts and the ability of the complexes to bind to the zinc-finger motif (in competition with zinc) was established. The results support a model whereby displacement of zinc from the PARP-1 zinc finger by other metal ions leads to decreased PARP-1 activity. In vitro combination studies of cisplatin with NAMI-A and RAPTA-T on different cancer cell lines (MCF7, A2780, and A2780cisR) showed that, in some cases, a synergistic effect is in operation.",

author = "Filipa Mendes and Michael Groessl and Nazarov, \{Alexey A.\} and Tsybin, \{Yury O.\} and Gianni Sava and Isabel Santos and Dyson, \{Paul J.\} and Angela Casini",

year = "2011",

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doi = "10.1021/jm2000135",

language = "English",

volume = "54",

pages = "2196--2206",

journal = "Journal of Medicinal Chemistry",

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T1 - Metal-based inhibition of poly(ADP-ribose) polymerase-the guardian angel of DNA

AU - Mendes, Filipa

AU - Groessl, Michael

AU - Nazarov, Alexey A.

AU - Tsybin, Yury O.

AU - Sava, Gianni

AU - Santos, Isabel

AU - Dyson, Paul J.

AU - Casini, Angela

PY - 2011/4/14

Y1 - 2011/4/14

N2 - The inhibition activity of a series of anticancer metal complexes based on platinum, ruthenium, and gold metal ions was evaluated on the zinc-finger protein PARP-1, either purified or directly on protein extracts from human breast cancer MCF7 cells. Information on the reactivity of the metal complexes with the PARP-1 zinc-finger domain was obtained by high-resolution ESI FT-ICR mass spectrometry. An excellent correlation between PARP-1 inhibition in protein extracts and the ability of the complexes to bind to the zinc-finger motif (in competition with zinc) was established. The results support a model whereby displacement of zinc from the PARP-1 zinc finger by other metal ions leads to decreased PARP-1 activity. In vitro combination studies of cisplatin with NAMI-A and RAPTA-T on different cancer cell lines (MCF7, A2780, and A2780cisR) showed that, in some cases, a synergistic effect is in operation.

AB - The inhibition activity of a series of anticancer metal complexes based on platinum, ruthenium, and gold metal ions was evaluated on the zinc-finger protein PARP-1, either purified or directly on protein extracts from human breast cancer MCF7 cells. Information on the reactivity of the metal complexes with the PARP-1 zinc-finger domain was obtained by high-resolution ESI FT-ICR mass spectrometry. An excellent correlation between PARP-1 inhibition in protein extracts and the ability of the complexes to bind to the zinc-finger motif (in competition with zinc) was established. The results support a model whereby displacement of zinc from the PARP-1 zinc finger by other metal ions leads to decreased PARP-1 activity. In vitro combination studies of cisplatin with NAMI-A and RAPTA-T on different cancer cell lines (MCF7, A2780, and A2780cisR) showed that, in some cases, a synergistic effect is in operation.

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JO - Journal of Medicinal Chemistry

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ER -

Metal-based inhibition of poly(ADP-ribose) polymerase-the guardian angel of DNA

Abstract

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