scholarly journals Selective Targeting of Class I Histone Deacetylases in a Model of Human Osteosarcoma

Cancers ◽  
2021 ◽  
Vol 13 (16) ◽  
pp. 4199
Author(s):  
Haydee M. Torres ◽  
Ashley M. VanCleave ◽  
Mykayla Vollmer ◽  
Dakota L. Callahan ◽  
Austyn Smithback ◽  
...  
Keyword(s):  
Cell Growth ◽  
Histone Deacetylases ◽  
Cell Function ◽  
Human Tumor ◽  
Class I ◽  
Osteosarcoma Cell ◽  
Immunodeficient Mice ◽  
Human Osteosarcoma

Dysregulation of histone deacetylases (HDACs) is associated with the pathogenesis of human osteosarcoma, which may present an epigenetic vulnerability as well as a therapeutic target. Domatinostat (4SC-202) is a next-generation class I HDAC inhibitor that is currently being used in clinical research for certain cancers, but its impact on human osteosarcoma has yet to be explored. In this study, we report that 4SC-202 inhibits osteosarcoma cell growth in vitro and in vivo. By analyzing cell function in vitro, we show that the anti-tumor effect of 4SC-202 involves the combined induction of cell-cycle arrest at the G2/M phase and apoptotic program, as well as a reduction in cell invasion and migration capabilities. We also found that 4SC-202 has little capacity to promote osteogenic differentiation. Remarkably, 4SC-202 revised the global transcriptome and induced distinct signatures of gene expression in vitro. Moreover, 4SC-202 decreased tumor growth of established human tumor xenografts in immunodeficient mice in vivo. We further reveal key targets regulated by 4SC-202 that contribute to tumor cell growth and survival, and canonical signaling pathways associated with progression and metastasis of osteosarcoma. Our study suggests that 4SC-202 may be exploited as a valuable drug to promote more effective treatment of patients with osteosarcoma and provide molecular insights into the mechanism of action of class I HDAC inhibitors.

Long non-coding RNA THOR promotes human osteosarcoma cell growth in vitro and in vivo

2018 ◽  
Vol 499 (4) ◽  
pp. 913-919 ◽  
Author(s):  
Wangzhen Chen ◽  
Meikai Chen ◽  
Yifan Xu ◽  
Xuerong Chen ◽  
Ping Zhou ◽  
...  
Keyword(s):  
Cell Growth ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Non Coding Rna ◽  
Human Osteosarcoma Cell ◽  
Long Non Coding Rna

scholarly journals Formononetin Induces Apoptosis of Human Osteosarcoma Cell Line U2OS by Regulating the Expression of Bcl-2, Bax and MiR-375 In Vitro and In Vivo

2015 ◽  
Vol 37 (3) ◽  
pp. 933-939 ◽  
Author(s):  
Wei Hu ◽  
ZengMing Xiao
Keyword(s):  
Cell Line ◽  
Cell Apoptosis ◽  
Osteosarcoma Cell Line ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma Cell Line ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell ◽  
U2os Cells

Background/Aims: Phytoestrogens are known to prevent tumor progression by inhibiting proliferation and inducing apoptosis in cancer cells. Formononetin is one of the main components of red clover plants, and is considered as a typical phytoestrogen. This study investigates formononetin induction of apoptosis of human osteosarcoma cell line U2OS by regulating Bcl-2 and Bax expression in vitro and in vivo. Methods: U2OS cells were treated with different concentrations of formononetin and the proliferation of the cells was measured using an MTT assay. Cell apoptosis was examined by flow cytometry. The levels of miR-375, Bax and Bcl-2 protein expression in treated cells were determined by Western blot and RT-PCR. The antitumor activity of formononetin was also evaluated in vivo in nude mice bearing orthotopic tumor implants. Results: High concentrations of formononetin significantly suppress the proliferation of U2OS cells and induce cell apoptosis. Moreover, compared to control group the expression of Bcl-2 and miR-375 decreases with formononetin in the U2OS cells, while Bax increases. Conclusion: Formononetin has inhibitory effects on the proliferation of U2SO cells, both in vitro and in vivo. This antitumor effect is directly correlated with formononetin concentration.

The bisphosphonate pamidronate is a potent inhibitor of human osteosarcoma cell growth in vitro

2001 ◽  
Vol 12 (5) ◽  
pp. 459-465 ◽  
Author(s):  
Jürgen Sonnemann ◽  
Vera Eckervogt ◽  
Borna Truckenbrod ◽  
Joachim Boos ◽  
Winfried Winkelmann ◽  
...  
Keyword(s):  
Cell Growth ◽  
Potent Inhibitor ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell

scholarly journals Positive regulation of plasmacytoid dendritic cell function via Ly49Q recognition of class I MHC

2008 ◽  
Vol 205 (13) ◽  
pp. 3187-3199 ◽  
Author(s):  
Lee-Hwa Tai ◽  
Marie-Line Goulet ◽  
Simon Belanger ◽  
Noriko Toyama-Sorimachi ◽  
Nassima Fodil-Cornu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Viral Infections ◽  
Plasmacytoid Dendritic Cell ◽  
Class I ◽  
Type I ◽  
Class I Mhc ◽  
Mhc Molecules

Plasmacytoid dendritic cells (pDCs) are an important source of type I interferon (IFN) during initial immune responses to viral infections. In mice, pDCs are uniquely characterized by high-level expression of Ly49Q, a C-type lectin-like receptor specific for class I major histocompatibility complex (MHC) molecules. Despite having a cytoplasmic immunoreceptor tyrosine-based inhibitory motif, Ly49Q was found to enhance pDC function in vitro, as pDC cytokine production in response to the Toll-like receptor (TLR) 9 agonist CpG-oligonucleotide (ODN) could be blocked using soluble monoclonal antibody (mAb) to Ly49Q or H-2Kb. Conversely, CpG-ODN–dependent IFN-α production by pDCs was greatly augmented upon receptor cross-linking using immobilized anti-Ly49Q mAb or recombinant H-2Kb ligand. Accordingly, Ly49Q-deficient pDCs displayed a severely reduced capacity to produce cytokines in response to TLR7 and TLR9 stimulation both in vitro and in vivo. Finally, TLR9-dependent antiviral responses were compromised in Ly49Q-null mice infected with mouse cytomegalovirus. Thus, class I MHC recognition by Ly49Q on pDCs is necessary for optimal activation of innate immune responses in vivo.

scholarly journals The Influence of Elementary Silver Versus Titanium on Osteoblasts Behaviour In Vitro Using Human Osteosarcoma Cell Lines

Sarcoma ◽  
2007 ◽  
Vol 2007 ◽  
pp. 1-5 ◽  
Author(s):  
Jendrik Hardes ◽  
Arne Streitburger ◽  
Helmut Ahrens ◽  
Thomas Nusselt ◽  
Carsten Gebert ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cell Function ◽  
Antimicrobial Effect ◽  
Proliferation Rate ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Significant Difference ◽  
Human Osteosarcoma Cell ◽  
Experimental Trials

Purpose. The antimicrobial effect of a silver-coated tumor endoprosthesis has been proven in clinical and experimental trials. However, in the literature there are no reports concerning the effect of elementary silver on osteoblast behaviour. Therefore, the prosthetic stem was not silver-coated because of concerns regarding a possible inhibition of the osseointegration. The aim of the present study was to investigate the effect of 5–25 mg of elementary silver in comparison to Ti-6Al-4V on human osteosarcoma cell lines (HOS- 58, SAOS).Methods. Cell viability was determined by measuring the MTT proliferation rate. Cell function was studied by measuring alkaline phosphatase (AP) activity and osteocalcine production.Results. In the HOS-58 cells, the AP activity was statistically significant(P<0.05)higher at a supplement of 5–10 mg of silver than of Ti-6 Al-4V at the same doses. For both cell lines, a supplement above 10 mg of silver resulted in a reduced AP activity in comparision to the Ti-6 Al-4V group, but a statistically significant difference(P<0.05)was observed at a dose of 25 mg for the SAOS cells only. At doses of 20–25 mg in the HOS-58 cells and 10–25 mg in the SAOS cells, the reduction of the proliferation rate by silver was statistically significant(P<0.05)compared to the Ti-6 Al-4V supplement.Discussion. In conclusion, elementary silver exhibits no cytotoxicity at low concentrations. In contrast, it seems to be superior to Ti-6 Al-4V concerning the stimulation of osteogenic maturation at these concentrations, whereas at higher doses it causes the known cytotoxic properties.

The bisphosphonates alendronate and zoledronate are inhibitors of canine and human osteosarcoma cell growth in vitro

2003 ◽  
Vol 1 (4) ◽  
pp. 207-215 ◽  
Author(s):  
V. J. Poirier ◽  
M. K. Huelsmeyer ◽  
I. D. Kurzman ◽  
D. H. Thamm ◽  
D. M. Vail
Keyword(s):  
Cell Growth ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cell

Synergistic effect of Apomine and Lovastatin on osteosarcoma cell growth in vitro and in vivo

Bone ◽  
2010 ◽  
Vol 46 ◽  
pp. S38
Author(s):  
Gatien Moriceau ◽  
Anke Roelofs ◽  
Regis Brion ◽  
F. Hal Ebetino ◽  
Mike J. Rogers ◽  
...  
Keyword(s):  
Cell Growth ◽  
Synergistic Effect ◽  
Osteosarcoma Cell

scholarly journals PROTAC induced-BET protein degradation exhibits potent anti-osteosarcoma activity by triggering apoptosis

2019 ◽  
Vol 10 (11) ◽  
Author(s):  
Chengcheng Shi ◽  
Huapeng Zhang ◽  
Penglei Wang ◽  
Kai Wang ◽  
Denghui Xu ◽  
...  
Keyword(s):  
Therapeutic Agent ◽  
Osteosarcoma Cell ◽  
Human Osteosarcoma ◽  
Bet Inhibitors ◽  
Oncogenic Protein ◽  
Bet Protein ◽  
Massive Apoptosis ◽  
Promising Therapeutic Agent

Abstract Targeting oncogenic proteins for degradation using proteolysis-targeting chimera (PROTAC) recently has drawn increasing attention in the field of cancer research. Bromodomain and extra-terminal (BET) family proteins are newly identified cancer-related epigenetic regulators, which have a role in the pathogenesis and progression of osteosarcoma. In this study, we investigated the in vitro and in vivo anti-osteosarcoma activity by targeting BET with a PROTAC molecule BETd-260. The results showed that BETd-260 completely depletes BET proteins and potently suppresses cell viability in MNNG/HOS, Saos-2, MG-63, and SJSA-1 osteosarcoma cell lines. Compared with BET inhibitors HJB-97 and JQ1, the activity of BETd-260 increased over 1000 times. Moreover, BETd-260 substantially inhibited the expression of anti-apoptotic Mcl-1, Bcl-xl while increased the expression of pro-apoptotic Noxa, which resulted in massive apoptosis in osteosarcoma cells within hours. In addition, pro-oncogenic protein c-Myc also was substantially inhibited by BETd-260 in the OS cells. Of note, BETd-260 induced degradation of BET proteins, triggered apoptosis in xenograft osteosarcoma tumor tissue, and profoundly inhibited the growth of cell-derived and patient-derived osteosarcoma xenografts in mice. Our findings indicate that BET PROTACs represent a promising therapeutic agent for human osteosarcoma.

scholarly journals HDAC Screening Identifies the HDAC Class I Inhibitor Romidepsin as a Promising Epigenetic Drug for Biliary Tract Cancer

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3862
Author(s):  
Christian Mayr ◽  
Tobias Kiesslich ◽  
Sara Erber ◽  
Dino Bekric ◽  
Heidemarie Dobias ◽  
...  
Keyword(s):  
Cell Viability ◽  
Cell Lines ◽  
Biliary Tract ◽  
Biliary Tract Cancer ◽  
Histone Deacetylases ◽  
Class I ◽  
In Vivo Evaluation ◽  
Tract Cancer

Inhibition of histone deacetylases (HDACs) is a promising anti-cancer approach. For biliary tract cancer (BTC), only limited therapeutic options are currently available. Therefore, we performed a comprehensive investigation of HDAC expression and pharmacological HDAC inhibition into a panel of eight established BTC cell lines. The screening results indicate a heterogeneous expression of HDACs across the studied cell lines. We next tested the effect of six established HDAC inhibitors (HDACi) covering pan- and class-specific HDACis on cell viability of BTC cells and found that the effect (i) is dose- and cell-line-dependent, (ii) does not correlate with HDAC isoform expression, and (iii) is most pronounced for romidepsin (a class I HDACi), showing the highest reduction in cell viability with IC50 values in the low-nM range. Further analyses demonstrated that romidepsin induces apoptosis in BTC cells, reduces HDAC activity, and increases acetylation of histone 3 lysine 9 (H3K9Ac). Similar to BTC cell lines, HDAC 1/2 proteins were heterogeneously expressed in a cohort of resected BTC specimens (n = 78), and their expression increased with tumor grading. The survival of BTC patients with high HDAC-2-expressing tumors was significantly shorter. In conclusion, HDAC class I inhibition in BTC cells by romidepsin is highly effective in vitro and encourages further in vivo evaluation in BTC. In situ assessment of HDAC 2 expression in BTC specimens indicates its importance for oncogenesis and/or progression of BTC as well as for the prognosis of BTC patients.

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