ATM kinase inhibition (CP466722) was also cytotoxic for both MCF-7 and SKBr-3 cells. Unlike NU1025, AZD2461, a new PARP-1 inhibitor, markedly reduced the numbers of living MCF-7 and SKBr-3 cells. Changes in cell cycle progression were monitored by flow cytometric measurement of DNA content in cells stained with propidium iodide. We 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. 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. These unexpected observations prompted speculation that other PARP-1 inhibitor(s) may be more cytotoxic towards SKBr-3 cells. 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. Cells harboring BRCA1/BRCA2 mutations are hypersensitive to inhibition of poly(ADP-ribose) polymerase-1 (PARP-1).
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