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Novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor as treatment for hepatocellular carcinoma.

Nakao K, Tanaka S, Miura T, Sato K, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Arii S, Tanabe M - Cancer Sci. (2015)

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

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In vitro effects of JNJ-28841072 in human hepatocellular carcinoma (HCC) cells. (a) Representative bar graphs show cell viability rates (%) after incubation with various concentrations of JNJ-28841072 in each cell line. Vertical bars indicate SD. (b) Cellular DNA content was analyzed by flow cytometry in four human HCC cell lines after 24 h of incubation with 3 μM JNJ-28841072 or control DMSO buffer; the increasing rate of >4N DNA (%) is indicated. (c) Immunocytochemistry of phosphohistone H3 (PhH3) in human HCC cells after 16 h of incubation with 3 μM JNJ-28841072 or control DMSO buffer. Magnification, ×40. (d) PhH3-positive rate (%) of high power field. Vertical bars indicate SE. Statistical analysis used two-tailed Student’s t-test (*P < 0.05).
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fig01: In vitro effects of JNJ-28841072 in human hepatocellular carcinoma (HCC) cells. (a) Representative bar graphs show cell viability rates (%) after incubation with various concentrations of JNJ-28841072 in each cell line. Vertical bars indicate SD. (b) Cellular DNA content was analyzed by flow cytometry in four human HCC cell lines after 24 h of incubation with 3 μM JNJ-28841072 or control DMSO buffer; the increasing rate of >4N DNA (%) is indicated. (c) Immunocytochemistry of phosphohistone H3 (PhH3) in human HCC cells after 16 h of incubation with 3 μM JNJ-28841072 or control DMSO buffer. Magnification, ×40. (d) PhH3-positive rate (%) of high power field. Vertical bars indicate SE. Statistical analysis used two-tailed Student’s t-test (*P < 0.05).

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).


Novel Aurora/vascular endothelial growth factor receptor dual kinase inhibitor as treatment for hepatocellular carcinoma.

Nakao K, Tanaka S, Miura T, Sato K, Matsumura S, Aihara A, Mitsunori Y, Ban D, Ochiai T, Kudo A, Arii S, Tanabe M - Cancer Sci. (2015)

In vitro effects of JNJ-28841072 in human hepatocellular carcinoma (HCC) cells. (a) Representative bar graphs show cell viability rates (%) after incubation with various concentrations of JNJ-28841072 in each cell line. Vertical bars indicate SD. (b) Cellular DNA content was analyzed by flow cytometry in four human HCC cell lines after 24 h of incubation with 3 μM JNJ-28841072 or control DMSO buffer; the increasing rate of >4N DNA (%) is indicated. (c) Immunocytochemistry of phosphohistone H3 (PhH3) in human HCC cells after 16 h of incubation with 3 μM JNJ-28841072 or control DMSO buffer. Magnification, ×40. (d) PhH3-positive rate (%) of high power field. Vertical bars indicate SE. Statistical analysis used two-tailed Student’s t-test (*P < 0.05).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4556391&req=5

fig01: In vitro effects of JNJ-28841072 in human hepatocellular carcinoma (HCC) cells. (a) Representative bar graphs show cell viability rates (%) after incubation with various concentrations of JNJ-28841072 in each cell line. Vertical bars indicate SD. (b) Cellular DNA content was analyzed by flow cytometry in four human HCC cell lines after 24 h of incubation with 3 μM JNJ-28841072 or control DMSO buffer; the increasing rate of >4N DNA (%) is indicated. (c) Immunocytochemistry of phosphohistone H3 (PhH3) in human HCC cells after 16 h of incubation with 3 μM JNJ-28841072 or control DMSO buffer. Magnification, ×40. (d) PhH3-positive rate (%) of high power field. Vertical bars indicate SE. Statistical analysis used two-tailed Student’s t-test (*P < 0.05).
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).

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.

View Article: PubMed Central - PubMed

Affiliation: Department of Molecular Oncology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.

Show MeSH
Related in: MedlinePlus