scholarly journals DEPDC1/ EEF1A1 Complex Promotes the Progression of Human Osteosarcoma via Downregulation of FOXO3a

2020 ◽  
Author(s):  
Lin Shen ◽  
Han Lin ◽  
Aijun Zhang ◽  
Ronghan Liu ◽  
Chendan Zhou ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Molecular Mechanisms ◽  
Mass Spectrometry Analysis ◽  
Osteosarcoma Cells ◽  
Critical Pathway ◽  
Spectrometry Analysis ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Abstract BackgroundOsteosarcoma is a common primary malignant bone tumor with poor prognosis. Currently there is no effective therapeutic strategies primarily due to the insufficient understanding its underlying mechanisms. Here we aimed to decipher the molecular mechanisms underlying the osteosarcoma progression.MethodsGEO data analysis, immunohistochemistry, qRT-PCR and western blotting were performed to evaluate the expression of differentially genes in human osteosarcoma tissues. Stably transfected human osteosarcoma cells were injected in mouse model to assess the effect of DEPDC1 in vivo. The function of DEPDC1–EEF1A1–FOXO3a axis was detected by mass spectrometry analysis, co-immunoprecipitation (co-IP) experiments and RNA sequencing in vitro. ResultsBy exploring differentially expressed genes, we found DEPDC1 is highly expressed in human osteosarcoma cells and tissues. Mechanistically, we found the protein expressed by DEPDC1 can directly bind to EEF1A1 through three binding regions, thus forming a complex. Importantly, DEPDC1/EEF1A1 complex can directly inhibit the transcription and expression of FOXO3a in vitro and in vivo, thus promoting the metastasis and proliferation of osteosarcoma. The clinical relevance study showed that overexpression of DEPDC1/EEF1A1 complex is correlated with reduced survival rate of osteosarcoma patients.ConclusionsCollectively, this study demonstrated the DEPDC1/EEF1A1–FOXO3a axis as a critical pathway that promotes the progression of osteosarcoma and leads to poor prognosis. Genetically targeting or pharmacologically inhibiting DEPDC1/EEF1A1–FOXO3a axis may serve a promising strategy for targeting human osteosarcoma.

scholarly journals Licochalcone A-Induced Apoptosis Through the Activation of p38MAPK Pathway Mediated Mitochondrial Pathways of Apoptosis in Human Osteosarcoma Cells In Vitro and In Vivo

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1441 ◽  
Author(s):  
Lin ◽  
Yang ◽  
Chiou ◽  
Hsieh ◽  
Wen ◽  
...  
Keyword(s):  
Cell Viability ◽  
Mitochondrial Membrane ◽  
Annexin V ◽  
Osteosarcoma Cells ◽  
Antitumor Effects ◽  
Licochalcone A ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Background: Licochalcone A (LicA) is isolated from the roots of Glycyrrhiza glabra and possesses antitumor and anti-invasive activities against several tumor cells. However, the antitumor effects of LicA on human osteosarcoma cells have yet to be demonstrated either in vitro or in vivo. Methods: Cell viability was measured by MTT assay. Apoptosis and mitochondrial dysfunction were detected with Annexin V/PI staining and JC-1 staining by flow cytometry. The expressions of caspase- or mitochondrial-related proteins were demonstrated by western blotting. Antitumor effect of LicA on 143B xenograft mice in vivo. Results: LicA could inhibit cell proliferation and induce apoptosis in human osteosarcoma cells, as evidenced by a decrease in cell viability, loss of mitochondrial membrane potentials, and activation of caspases. LicA treatment substantially reduced the expression of Bcl-2 and Mcl-1 and increased the expression of cleaved-caspase-3, cleaved-caspase-9, cleaved-PARP, and Bax in HOS and U2OS cells. Moreover, mitochondrial membrane potential and apoptosis suppression mediated by Z-VAD or tauroursodeoxycholic acid significantly reduced LicA-induced mitochondria-dependent apoptosis. The study also determined that LicA treatment induced p38MAPK phosphorylation, but siRNA-p38 or BIRB796 substantially reversed cell viability through the inhibition of mitochondria-dependent apoptosis pathways. Finally, an in vivo study revealed that LicA significantly inhibited 143B xenograft tumor growth. Conclusions: These findings demonstrate that LicA has antitumor activities against human osteosarcoma cells through p38MAPK regulation of mitochondria-mediated intrinsic apoptotic pathways in vitro and in vivo.

scholarly journals Extracellular Nanovesicles Secreted by Human Osteosarcoma Cells Promote Angiogenesis

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 779 ◽  
Author(s):  
Francesca Perut ◽  
Laura Roncuzzi ◽  
Nicoletta Zini ◽  
Annamaria Massa ◽  
Nicola Baldini
Keyword(s):  
Endothelial Cell ◽  
Chorioallantoic Membrane ◽  
Tube Formation ◽  
Osteosarcoma Cells ◽  
Cell Functions ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Neutral Conditions

Angiogenesis involves a number of different players among which extracellular nanovesicles (EVs) have recently been proposed as an efficient cargo of pro-angiogenic mediators. Angiogenesis plays a key role in osteosarcoma (OS) development and progression. Acidity is a hallmark of malignancy in a variety of cancers, including sarcomas, as a result of an increased energetic metabolism. The aim of this study was to investigate the role of EVs derived from osteosarcoma cells on angiogenesis and whether extracellular acidity, generated by tumor metabolism, could influence EVs activity. For this purpose, we purified and characterized EVs from OS cells maintained at either acidic or neutral pH. The ability of EVs to induce angiogenesis was assessed in vitro by endothelial cell tube formation and in vivo using chicken chorioallantoic membrane. Our findings demonstrated that EVs derived from osteosarcoma cells maintained either in acidic or neutral conditions induced angiogenesis. The results showed that miRNA and protein content of EVs cargo are correlated with pro-angiogenic activity and this activity is increased by the acidity of tumor microenvironment. This study provides evidence that EVs released by human osteosarcoma cells act as carriers of active angiogenic stimuli that are able to promote endothelial cell functions relevant to angiogenesis.

scholarly journals Antitumor effects of pristimerin on human osteosarcoma cells in vitro and in vivo

2017 ◽  
Vol Volume 10 ◽  
pp. 5703-5710 ◽  
Author(s):  
Yuki Mori ◽  
Toshiharu Shirai ◽  
Ryu Terauchi ◽  
Shinji Tsuchida ◽  
Naoki Mizoshiri ◽  
...  
Keyword(s):  
Osteosarcoma Cells ◽  
Antitumor Effects ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

scholarly journals Imperatorin induces autophagy and G0/G1 phase arrest via PTEN-PI3K-AKT-mTOR/p21 signaling pathway in human osteosarcoma cells in vitro and in vivo

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Minchao Lv ◽  
Qingxin Xu ◽  
Bei Zhang ◽  
Zhiqiang Yang ◽  
Jun Xie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Bioinformatic Analysis ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Cycle Arrest ◽  
Phase Arrest ◽  
Human Osteosarcoma Cells ◽  
G1 Phase Arrest

Abstract Background Osteosarcoma is the third most common cancer in adolescence and the first common primary malignant tumor of bone. The long-term prognosis of osteosarcoma still remains unsatisfactory in the past decades. Therefore, development of novel therapeutic agents which are effective to osteosarcoma and are safe to normal tissue simultaneously is quite essential and urgent. Methods Firstly, MTT assay, cell colony formation assay, cell migration and invasion assays were conducted to evaluate the inhibitory effects of imperatorin towards human osteosarcoma cells. RNA-sequence assay and bioinformatic analysis were then performed to filtrate and assume the potential imperatorin-induced cell death route and signaling pathway. Moreover, quantitative real-time PCR assay, western blot assay and rescue experiments were conducted to confirm the assumptions of bioinformatic analysis. Finally, a subcutaneous tumor-transplanted nude mouse model was established and applied to evaluate the internal effect of imperatorin on osteosarcoma by HE and immunohistochemistry staining. Results Imperatorin triggered time-dependent and dose-dependent inhibition of tumor growth mainly by inducing autophagy promotion and G0/G1 phase arrest in vitro and in vivo. Besides, imperatorin treatment elevated the expression level of PTEN and p21, down-regulated the phosphorylation of AKT and mTOR. In contrast, the inhibition of PTEN using Bpv (HOpic), a potential and selective inhibitor of PTEN, concurrently rescued imperatorin-induced autophagy promotion, cell cycle arrest and inactivation of PTEN-PI3K-AKT-mTOR/p21 pathway. Conclusions This work firstly revealed that imperatorin induced autophagy and cell cycle arrest through PTEN-PI3K-AKT-mTOR/p21 signaling pathway by targeting and up-regulating PTEN in human osteosarcoma cells. Hence, imperatorin is a desirable candidate for clinical treatments of osteosarcoma.

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