scholarly journals DEPDC1/ EEF1A1 complex promotes the progression of human osteosarcoma via downregulation of FOXO3a

2021 ◽  
Author(s):  
Lin Shen ◽  
Han Li ◽  
Aijun Zhang ◽  
Ronghan Liu ◽  
Chendan Zhou ◽  
...  
Keyword(s):  
Tumor Metastasis ◽  
Profile Analysis ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Critical Pathway ◽  
Human Osteosarcoma ◽  
Expression Profile Analysis ◽  
Tumor Tissues ◽  
Human Osteosarcoma Cells ◽  
Patient Survival Rate

This study deciphers a potentially critical interplay of DEPDC1-EEF1A1-FOXO3a axis during the osteosarcoma progression. Bioinformatics analysis of documented 25,035 genes for differentially expressed genes were accompanied by transcriptional and translational examinations of clinical osteosarcoma specimens and osteosarcoma cell lines to assess the roles and interactions of DEPDC1, EEF1A1, and FOXO3a in the tumor cells proliferation and prognosis. Gene expression profile analysis and clinical tests revealed highly expressed DEPDC1 in human osteosarcoma cells and tumor tissues. Vector-mediated silence of DEPDC1 resulted in halted osteosarcoma cell proliferation, promoted apoptosis, and ceased tumor metastasis. Immunoprecipitation assay confirmed that EEF1A1 directly bind to DEPDC1 protein through three binding regions. Further, DEPDC1/EEF1A1 complex significantly decreased the expression of FOXO3a at transcription and translation levels, which subsequently promoted the proliferation of osteosarcoma cells and tumor metastasis. Correlation studies exhibited that overexpression of DEPDC1/EEF1A1 complex in the clinical specimens negatively correlated with the patient survival rate. In conclusion, DEPDC1-EEF1A1-FOXO3a axis plays as a critical pathway that regulates the progression and prognosis of osteosarcoma.

scholarly journals Antiproliferative Properties of Oleuropein in Human Osteosarcoma Cells

2016 ◽  
Vol 11 (4) ◽  
pp. 1934578X1601100 ◽  
Author(s):  
Jose M. Moran ◽  
Olga Leal-Hernandez ◽  
Maria L. Canal-Macías ◽  
Raul Roncero-Martin ◽  
Rafael Guerrero-Bonmatty ◽  
...  
Keyword(s):  
Cell Lines ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Probit Regression ◽  
Cytotoxic Effects ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Mg63 Cells ◽  
Human Osteosarcoma Cell

In this study, we evaluated the antiproliferative activity on two human osteosarcoma cell lines (MG-63 and Saos2) of oleuropein, an olive oil compound traditionally found in the Mediterranean diet. Oleuropein exhibited obvious cytotoxic effects on human osteosarcoma cells in a concentration- and time-dependent manner. Statistical analysis of IC50 by the Probit regression method suggested that oleuropein had similar toxic effects on both cell lines tested (IC50 range from 247.4–475.0 μM for MG63 cells and from 798.7–359.9 μM for Saos2 cells).

scholarly journals Micro-RNA 122 and micro-RNA 96 affected human osteosarcoma biological behavior and associated with prognosis of patients with osteosarcoma

2020 ◽  
Vol 40 (12) ◽  
Author(s):  
Bin Liu ◽  
Shuqiang Yao ◽  
Jiping Zhou
Keyword(s):  
Independent Predictor ◽  
Micro Rna ◽  
Biological Behavior ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Rt Pcr ◽  
Normal Tissues ◽  
Human Osteosarcoma ◽  
Tumor Tissues ◽  
Human Osteosarcoma Cell

Abstract Osteosarcoma (OS) is the most common bone malignancy in both children and adolescents. In the present study, we aimed to explore the association of miRNA-122 and miRNA-96 expression with the clinical characteristics and prognosis of patients with osteosarcoma. The expression of miRNA-122 and miRNA-96 in human osteosarcoma cell lines and tissues were detected in the present study. Reverse transcriptase-PCR (RT-PCR) was used to determine the expression levels of miRNA-122 and miRNA-96 in 68 human OS samples. We found that MiRNA-122 and miRNA-96 were widely up-regulated in osteosarcoma, gastric cancer and pancreatic cancer. In HOS, Saos-2 and U2OS osteosarcoma cells, miRNA-122 and miRNA-96 were up-regulated significantly, while down-regulated in MG-63 cells. After further investigation, we found that miRNA-122 and miRNA-96 concentrations were significantly higher in the tumor tissues than those in the normal tissues (P<0.01). Moreover, the cell proliferation of LV-miRNA-122-RNAi and LV-miRNA-96-RNAi transfected SaOS2 was significantly decreased compared with the LV- miRNA-122-RNAi-CN and LV- miRNA-96-RNAi group. After adjusting for competing risk factors, we found combined high miRNA-122 and miRNA-96 expression was identified as independent predictor of overall survival.

Neohesperidin Induces Cell Cycle Arrest, Apoptosis, and Autophagy via the ROS/JNK Signaling Pathway in Human Osteosarcoma Cells

2021 ◽  
pp. 1-24
Author(s):  
Shubin Wang ◽  
Zongguang Li ◽  
Wei Liu ◽  
Guojun Wei ◽  
Naichun Yu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Flow Cytometry ◽  
Signaling Pathway ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Jnk Signaling ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Jnk Signaling Pathway ◽  
Induced Apoptosis

Neohesperidin has anti-oxidative and anti-inflammatory properties and exerts extensive therapeutic effects on various cancers. In this study, the osteosarcoma cell lines were exposed to different concentrations of neohesperidin. Cell proliferation and viability were assessed by CCK-8 and colony-formation assays. The role of neohesperidin in cell cycle progression and apoptosis were analyzed by flow cytometry and western blotting. To identify autophagosomes and autolysosomes, we used a tandem GFP-mRFP-LC3B lentiviral construct. In addition, autophagy was evaluated by examining autophagosome formation using transmission electron microscopy. Intracellular reactive oxygen species (ROS) production was detected by fluorescence microscopy and flow cytometry. Subsequently, the activation of the ROS/JNK signaling pathway was investigated. Neohesperidin could inhibit proliferation and induce apoptosis in SJSA and HOS cells. The formation of autophagosomes indicated that autophagy occurred in neohesperidin-treated cells and the apoptotic effect of neohesperidin was significantly increased after the use of autophagy inhibitors. Subsequently, we found that neohesperidin-induced apoptosis and autophagy were related to the increase in ROS generation and were significantly inhibited by GSH. Moreover, neohesperidin induced activation of the c-Jun N-terminal kinase (JNK) signaling pathway and inhibition of JNK with SP600125 attenuated neohesperidin-induced apoptosis and autophagy simultaneously. Our data indicated that neohesperidin caused G2/M phase arrest and induced apoptosis and autophagy by activating the ROS/JNK pathway in human osteosarcoma cells, suggesting that neohesperidin is a potential drug candidate for the treatment of osteosarcomas.

scholarly journals β-Phenethyl Isothiocyanate Induces Cell Death in Human Osteosarcoma through Altering Iron Metabolism, Disturbing the Redox Balance, and Activating the MAPK Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-23
Author(s):  
Huanhuan Lv ◽  
Chenxiao Zhen ◽  
Junyu Liu ◽  
Peng Shang
Keyword(s):  
Oxidative Stress ◽  
Cell Death ◽  
Iron Metabolism ◽  
Ros Generation ◽  
Osteosarcoma Cell ◽  
Phenethyl Isothiocyanate ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Human Osteosarcoma Cell

Osteosarcoma is the most common primary malignancy of the skeleton in children and adults. The outcomes of people with osteosarcomas are unsatisfied. β-Phenethyl isothiocyanate (PEITC) exhibits chemoprevention and chemotherapeutic activities against many human cancers. The molecular mechanism underlying its action on osteosarcoma is still unknown. This study was aimed at investigating the effect of PEITC on human osteosarcoma both in vitro and in vivo. The results showed that PEITC reduced cell viability, inhibited proliferation, and caused G2/M cell cycle arrest in four human osteosarcoma cell lines (MNNG/HOS, U-2 OS, MG-63, and 143B). Then, we found that PEITC altered iron metabolism related to the processes of iron import, storage, and export, which resulted in increased labile iron. Expectedly, PEITC caused oxidative stress as a consequence of GSH depletion-inducing ROS generation and lipid peroxidation. Multiple cell death modalities, including ferroptosis, apoptosis, and autophagy, were triggered in human osteosarcoma cells. Three MAPKs (ERK, p38, and JNK) were all activated after PEITC treatment; however, they presented different responses among the four human osteosarcoma cell lines. ROS generation was proved to be the major cause of PEITC-induced decreased proliferative potential, altered iron metabolism, cell death, and activated MAPKs in human osteosarcoma cells. In addition, PEITC also significantly delayed tumor growth in a xenograft osteosarcoma mouse model with a 30 mg/kg administration dose. In conclusion, this study reveals that PEITC simultaneously triggers ferroptosis, apoptosis, and autophagy in human osteosarcoma cells by inducing oxidative stress.

scholarly journals Presence and activity of alkaline phosphatase in two human osteosarcoma cell lines.

1989 ◽  
Vol 37 (7) ◽  
pp. 1069-1074 ◽  
Author(s):  
J C Randall ◽  
D C Morris ◽  
S Zeiger ◽  
K Masuhara ◽  
T Tsuda ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Cell Membrane ◽  
Phosphatase Activity ◽  
Alkaline Phosphatase Activity ◽  
Osteogenic Sarcoma ◽  
Ultrastructural Level ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

The presence and activity of alkaline phosphatase in SAOS-2 and TE-85 human osteosarcoma cells grown in culture were examined at the ultrastructural level. A monoclonal antibody raised against purified human bone osteosarcoma alkaline phosphatase was used to localize the enzyme in cultures of the osteosarcoma cells. Similar cultures were analyzed for alkaline phosphatase activity using an enzyme cytochemical method with cerium as the capture agent. Alkaline phosphatase was immunolocalized at the light microscopic level in an osteogenic sarcoma and ultrastructurally on the SAOS-2 cell membrane and the enclosing membrane of extracellular vesicular structures close to the cells. In contrast, the TE-85 cells were characterized by the absence of all but a few traces of immunolabeling at the cell surface. Enzyme cytochemical studies revealed strong alkaline phosphatase activity on the outer surface of the SAOS-2 cell membrane. Much lower enzyme activity was observed in the TE-85 cells. The results support biochemical data from previous studies and confirm that SAOS-2 cells have a significantly greater concentration of alkaline phosphatase at the plasma membrane.

Effects of Iron Chelation in Osteosarcoma

2020 ◽  
Vol 20 ◽  
Author(s):  
Maura Argenziano ◽  
Alessandra Di Paola ◽  
Chiara Tortora ◽  
Daniela Di Pinto ◽  
Elvira Pota ◽  
...  
Keyword(s):  
Tumor Progression ◽  
Cancer Progression ◽  
Cell Cycle Progression ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Background: Osteosarcoma is an aggressive bone tumor. Itrepresents the principal cause of cancer-associated death in children.Considering the recent findings on the role of iron in cancer, iron chelation has been investigated for its antineoplastic properties in many tumors. Deferasirox is the most used iron chelator compound and in previous studies showed an anticancer effectinhematologic and solid malignancies. Eltrombopag is a Thrombopoietin receptor used in thrombocytopenia, that also binds and mobilize iron. It demonstrated an effect in iron overload conditions and also in contrasting cancer cells proliferation. Objective: We analyzed the effects of Deferasirox and Eltrombopag in Human Osteosarcoma cells, in the attempt to identify other therapeutic approaches for this tumor. Methods: We cultured and treated withDeferasirox and Eltrombopag, alone and in combination, two human osteosarcoma cell lines, MG63 and 143B. After 72h exposure, we performed RTqPCR, Western Blotting, Iron Assay and cytofluorimetric assays to evaluate the effect on viability, apoptosis, cell cycle progression and ROS production. Results: The iron chelating properties of the two compounds are confirmed also in Osteosarcoma, but we did not observe any direct effect on tumor progression. Discussion: We tested Deferasirox and Eltrombopag, alone and in combination, in Human Osteosarcoma cells for the first time and demonstrated that their iron chelating activity does not influence biochemical pathways related to cancer progression and maintenance. Conclusion: Although further investigations on possible effects mediated by cells of the tumor microenvironment could be of great interest, in vitro iron chelation in Osteosarcoma does not impair tumor progression.

scholarly journals Bioinspired-Metalloporphyrin Magnetic Nanocomposite as a Reusable Catalyst for Synthesis of Diastereomeric (−)-Isopulegol Epoxide: Anticancer Activity Against Human Osteosarcoma Cells (MG-63)

Molecules ◽  
2018 ◽  
Vol 24 (1) ◽  
pp. 52 ◽  
Author(s):  
Lucas Dias ◽  
Ana Batista de Carvalho ◽  
Sara Pinto ◽  
Gilberto Aquino ◽  
Mário Calvete ◽  
...  
Keyword(s):  
Reusable Catalyst ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma Cell Line ◽  
Anticancer Effect ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Human Osteosarcoma Cell ◽  
Ic50 Values

In the present study, we developed a green epoxidation approach for the synthesis of the diastereomers of (−)-isopulegol benzyl ether epoxide using molecular oxygen as the oxidant and a hybrid manganese(III)-porphyrin magnetic reusable nanocomposite as the catalyst. High activity, selectivity, and stability were obtained, with up to four recycling cycles without the loss of activity and selectivity for epoxide. The anticancer effect of the newly synthesized isopulegol epoxide diastereomers was evaluated on a human osteosarcoma cell line (MG-63); both diastereomers showed similar in vitro potency. The measured IC50 values were significantly lower than those reported for other monoterpene analogues, rendering these epoxide isomers as promising anti-tumor agents against low prognosis osteosarcoma.

scholarly journals Diallyl Disulfide Induces Apoptosis and Autophagy in Human Osteosarcoma MG-63 Cells through the PI3K/Akt/mTOR Pathway

Molecules ◽  
2019 ◽  
Vol 24 (14) ◽  
pp. 2665 ◽  
Author(s):  
Ziqi Yue ◽  
Xin Guan ◽  
Rui Chao ◽  
Cancan Huang ◽  
Dongfang Li ◽  
...  
Keyword(s):  
Annexin V ◽  
Mtor Pathway ◽  
Diallyl Disulfide ◽  
Osteosarcoma Cell ◽  
Dependent Manner ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
M Phase ◽  
Induced Apoptosis

Diallyl disulfide (DADs), a natural organic compound, is extracted from garlic and scallion and has anti-tumor effects against various tumors. This study investigated the anti-tumor activity of DADs in human osteosarcoma cells and the mechanisms. MG-63 cells were exposed to DADs (0, 20, 40, 60, 80, and 100 μM) for different lengths of time (24, 48, and 72 h). The CCK8 assay results showed that DADs inhibited osteosarcoma cell viability in a dose-and time-dependent manner. FITC-Annexin V/propidium iodide staining and flow cytometry demonstrated that the apoptotic ratio increased and the cell cycle was arrested at the G2/M phase as the DADs concentration was increased. A Western blot analysis was employed to detect the levels of caspase-3, Bax, Bcl-2, LC3-II/LC3-I, and p62 as well as suppression of the mTOR pathway. High expression of LC3-II protein revealed that DADs induced formation of autophagosome. Furthermore, DADs-induced apoptosis was weakened after adding 3-methyladenine, demonstrating that the DADs treatment resulted in autophagy-mediated death of MG-63 cells. In addition, DADs depressed p-mTOR kinase activity, and the inhibited PI3K/Akt/mTOR pathway increased DADs-induced apoptosis and autophagy. In conclusion, our results reveal that DADs induced G2/M arrest, apoptosis, and autophagic death of human osteosarcoma cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

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 Genome-wide analyses of XRN1-sensitive targets in osteosarcoma cells identifies disease-relevant transcripts containing G-rich motifs

2020 ◽  
Author(s):  
Amy L. Pashler ◽  
Benjamin P. Towler ◽  
Christopher I. Jones ◽  
Tom Burgess ◽  
Sarah F. Newbury
Keyword(s):  
Developmental Pathways ◽  
Osteosarcoma Cell ◽  
Rna Seq ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Genome Wide ◽  
Human Osteosarcoma Cells ◽  
Non Coding Rnas ◽  
Post Transcriptional Regulation ◽  
Bioinformatic Approach

ABSTRACTXRN1 is a highly conserved exoribonuclease which degrades uncapped RNAs in a 5’-3’ direction. Degradation of RNAs by XRN1 is important in many cellular and developmental processes and is relevant to human disease. Studies in D. melanogaster demonstrate that XRN1 can target specific RNAs, which have important consequences for developmental pathways. Osteosarcoma is a malignancy of the bone and accounts for 2% of all paediatric cancers worldwide. 5 year survival of patients has remained static since the 1970s and therefore furthering our molecular understanding of this disease is crucial. Previous work has shown a downregulation of XRN1 in osteosarcoma cells, however the transcripts regulated by XRN1 which might promote osteosarcoma remain elusive. Here, we confirm reduced levels of XRN1 in osteosarcoma cell lines and patient samples and identify XRN1-sensitive transcripts in human osteosarcoma cells. Using RNA-seq in XRN1-knockdown SAOS-2 cells, we show that 1178 genes are differentially regulated. Using a novel bioinformatic approach, we demonstrate that 134 transcripts show characteristics of direct post-transcriptional regulation by XRN1. Long non-coding RNAs (lncRNAs) are enriched in this group suggesting that XRN1 normally plays an important role in controlling lncRNA expression in these cells. Among potential lncRNAs targeted by XRN1 is HOTAIR, which is known to be upregulated in osteosarcoma and contribute to disease progression. We have also identified G-rich and GU motifs in post-transcriptionally regulated transcripts which appear to sensitise them to XRN1 degradation. Our results therefore provide significant insights into the specificity of XRN1 in human cells which is relevant to disease.

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