leupeptins and Bone-Neoplasms

leupeptins has been researched along with Bone-Neoplasms* in 4 studies

Other Studies

4 other study(ies) available for leupeptins and Bone-Neoplasms

ArticleYear
Transcriptional regulation of Runx2 by HSP90 controls osteosarcoma apoptosis via the AKT/GSK-3β/β-catenin signaling.
    Journal of cellular biochemistry, 2018, Volume: 119, Issue:1

    Osteosarcoma (OS) is the most malignant primary bone tumor in children and adolescents with limited treatment options and poor prognosis. Recently, aberrant expression of Runx2 has been found in OS, thereby contributing to the development, and progression of OS. However, the upstream signaling molecules that regulate its expression in OS remain largely unknown. In the present study, we first confirmed that the inhibition of HSP90 with 17-AAG caused significant apoptosis of OS cells via a caspase-3-dependent mechanism, and that inhibition or knockdown of HSP90 by 17-AAG or siRNAs significantly suppressed mRNA and protein expression of Runx2. Furthermore, we provided evidence that Runx2 was transcriptionally regulated by HSP90 when using MG132 and CHX chase assay. We also demonstrated that β-catenin was overexpressed in OS tissue, and that knockdown of β-catenin induced pronounced apoptosis of OS cells in the presence or absence of 17-AAG. Interestingly, this phenomenon was accompanied with a significant reduction of Runx2 and Cyclin D1 expression, indicating an essential role of Runx2/Cyclin D1 in 17-AAG-induced cells apoptosis. Moreover, we demonstrated that the apoptosis of OS cells induced by 17-AAG did require the involvement of the AKT/GSK-3β/β-catenin signaling pathway by using pharmacological inhibitor GSK-3β (LiCl) or siGSK-3β. Our findings reveal a novel mechanism that Runx2 is transcriptionally regulated by HSP90 via the AKT/GSK-3β/β-catenin signaling pathway, and by which leads to apoptosis of OS cells.

    Topics: Benzoquinones; beta Catenin; Bone Neoplasms; Cell Line, Tumor; Cell Survival; Core Binding Factor Alpha 1 Subunit; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3 beta; HSP90 Heat-Shock Proteins; Humans; Lactams, Macrocyclic; Leupeptins; Osteosarcoma; Proto-Oncogene Proteins c-akt; Signal Transduction; Transcription, Genetic

2018
Proteasome Inhibitor MG132 Enhances Cisplatin-Induced Apoptosis in Osteosarcoma Cells and Inhibits Tumor Growth.
    Oncology research, 2018, May-07, Volume: 26, Issue:4

    Topics: Animals; Antineoplastic Agents; Bone Neoplasms; Cell Line, Tumor; Cell Proliferation; Cell Survival; Cisplatin; Dose-Response Relationship, Drug; Drug Synergism; Humans; Leupeptins; Mice, Inbred BALB C; Mice, Nude; Osteosarcoma; Proteasome Inhibitors; Xenograft Model Antitumor Assays

2018
Proteasome inhibitor MG132 enhances TRAIL-induced apoptosis and inhibits invasion of human osteosarcoma OS732 cells.
    Biochemical and biophysical research communications, 2013, Sep-20, Volume: 439, Issue:2

    MG132 as a proteasome inhibitor could induce apoptosis in various cancer cells. This study aimed to discuss the effect of proteasome inhibitor MG132 on the TRAIL-induced apoptosis of human osteosarcoma OS732 cells. MG132 and TRAIL were applied on OS732 cells respectively or jointly. Cell survival rates, changes of cellular shape, cell apoptosis and cell invasion were analyzed, respectively, by 3-(4,5)-dimethylthiahiazo(-z-y1)-2,5-di-phenytetrazoliumromide (MTT) assay, inverted phase contrast microscope, flow cytometry, and transwell invasion chamber methods. The protein levels of DR5, caspase-3, caspase-8, p27(kip1) and MMP-9 were measured by Western blot analysis. The results indicated that combination of MG132 and TRAIL had the effect of up-regulating expression of DR5, caspase-3, caspase-8 and p27(kip1), down-regulating expression of MMP-9 and inducing apoptosis as well as suppressing the ability of invasion of OS732 cells. The survival rate of combined application of 10 μM MG132 and 100 ng/ml TRAIL on OS732 cells was significantly lower than that of the individual application (p<0.01). Changes of cellular shape and apoptotic rates also indicated the apoptosis-inducing effect of combined application was much stronger than that of individual application. Cell cycle analysis showed combination of MG132 and TRAIL mostly caused OS732 cells arrested at G2-M-phase. The invasion ability of OS732 cells was restrained significantly in the combined group compared with the individual group and control group.

    Topics: Antineoplastic Agents; Bone and Bones; Bone Neoplasms; Caspase 3; Caspase 8; Cell Cycle; Cell Line, Tumor; Drug Synergism; G2 Phase Cell Cycle Checkpoints; Humans; Leupeptins; M Phase Cell Cycle Checkpoints; Neoplasm Invasiveness; Osteosarcoma; Proteasome Inhibitors; Receptors, TNF-Related Apoptosis-Inducing Ligand; TNF-Related Apoptosis-Inducing Ligand

2013
Caspase-8 dependent osteosarcoma cell apoptosis induced by proteasome inhibitor MG132.
    Cell biology international, 2007, Volume: 31, Issue:10

    Many researchers have reported that proteasome inhibitors could induce apoptosis in a variety of cancer cells, such as breast cancer cell, lung cancer cell, and lymphoma cell. However, the effect of proteasome inhibitors on osteocsarcoma cells and the mechanisms are seldom studied. In this study, we found proteasome inhibitor MG132 was an effective inducer of apoptosis in human osteosarcoma MG-63 cells. On normal human diploid fibroblast cells, MG132 did not show any apoptosis-inducing effects. Apoptotic changes such as DNA fragment and apoptotic body were observed in MG132-treated cells and MG132 mostly caused MG-63 cell arrest at G(2)-M-phase by cell cycle analysis. Increased activation of caspase-8, accumulation of p27(Kip1), and an increased ratio of Bax:Bcl-2 were detected by RT-PCR and Western blot analysis. Activation of caspase-3 and caspase-9 were not observed. This suggests that the apoptosis induced by MG132 in MG63 cells is caspase-8 dependent, p27 and bcl-2 family related.

    Topics: Apoptosis; bcl-2-Associated X Protein; bcl-X Protein; Blotting, Western; Bone Neoplasms; Caspase 8; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p27; Cysteine Proteinase Inhibitors; Fibroblasts; Humans; Leupeptins; Osteosarcoma; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

2007
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