ArticleJournal of cancer prevention2014
Interactions Between Ataxia Telangiectasia Mutated Kinase Inhibition, Poly(ADP-ribose) Polymerase-1 Inhibition and BRCA1 Status in Breast Cancer Cells.
Article in Journal of cancer prevention, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
2 citing papers in PubMed, 6 citations in OpenAlex.
- [Effect and Mechanism of Radiosensitization of Poly (ADP-Ribose) Polymerase Inhibitor n Lewis Cells and Xenografts].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2016Article
- DNA Damage Signalling and Repair Inhibitors: The Long-Sought-After Achilles' Heel of Cancer.Biomolecules · 2015Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCells harboring BRCA1/BRCA2 mutations are hypersensitive to inhibition of poly(ADP-ribose) polymerase-1 (PARP-1). We recently showed that interference with PARP-1 activity by NU1025 is strongly cytotoxic for BRCA1-positive BT-20 cells but not BRCA1-deficient SKBr-3 cells. These unexpected observations prompted speculation that other PARP-1 inhibitor(s) may be more cytotoxic towards SKBr-3 cells. In addition, interference with the DNA damage signaling pathway via (for instance) Ataxia telangiectasia mutated (ATM) kinase inhibition may induce synthetic lethality in DNA repair-deficient breast cancer cells and pharmacological interference with ATM activity may sensitize breast cancer cells to PARP-1 inactivation.
methodsWe determined drug cytotoxicity in human MCF-7 and SKBr-3 breast cancer cells using the CellTiterGLO Luminescent cell viability assay and a Tecan multi-label, multitask plate counter to measure generated luminescence. Changes in cell cycle progression were monitored by flow cytometric measurement of DNA content in cells stained with propidium iodide.
resultsUnlike NU1025, AZD2461, a new PARP-1 inhibitor, markedly reduced the numbers of living MCF-7 and SKBr-3 cells. ATM kinase inhibition (CP466722) was also cytotoxic for both MCF-7 and SKBr-3 cells. Furthermore, AZD2461 enhanced the cytotoxicity of CP466722 in both cell lines by inducing apoptosis, and concurrent inhibition of ATM and PARP-1 reduced cell proliferation more strongly than either single treatment.
conclusionsOur data show that inhibition of PARP-1 by AZD2461 is synthetically lethal for NU1025-resistant MCF-7 and SKBr-3 breast cancer cells. They also indicate that DNA damage signaling is essential for survival of both SKBr-3 and MCF-7 cells, especially after inactivation of PARP-1.
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