Novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor as treatment for hepatocellular carcinoma.
Bottom Line: JNJ-28841072 suppressed in vitro phosphorylation of histone H3 with induction of cell polyploidy and death in a dose-dependent manner (IC50 = 0.8-1.2 μM).Our preclinical studies indicate that JNJ-28841072 is a promising novel therapeutic approach for the treatment of HCC.It might be worthy of evaluation in further studies.
Affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.Show MeSH
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Mentions: To evaluate the growth inhibitory effects of JNJ-28841072, cell proliferation assays were carried out in HCC cell lines (HuH-7, SK-Hep1, HLF, and Hep3B). JNJ-28841072 showed potent antiproliferative activity in all HCC cell types with the following IC50 values: HuH-7, 1.4 ± 0.3 μM; SK-Hep1, 1.2 ± 0.2 μM; HLF, 1.4 ± 0.2 μM; and Hep3B, 0.75 ± 0.15 μM (Fig.1a). Alterations in DNA ploidy in the human HCC cell lines were analyzed by flow cytometry. Accumulation of cells with >4N DNA content was observed in all of the cell lines following 24-h incubation with 3 μM JNJ-28841072 (HuH-7, 52.42 ± 2.8%; SK-Hep1, 65.82 ± 2.6%; HLF, 58.17 ± 2.9%; Hep3B, 63.17 ± 2.0%). The accumulation of polyploid cells is consistent with failed cytokinesis following inhibition of Aurora B kinase activity (Fig.1b).
Affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.