Apigenin Induces Apoptosis through Mitochondrial Dysfunction in U-2 OS Human Osteosarcoma Cells and Inhibits Osteosarcoma Xenograft Tumor Growth in Vivo

Timosaponin AIII (TSAIII) is a steroidal saponin which demonstrates anti-tumour activities. However, the effect of TSAIII on human osteosarcoma cells remains largely unknown. In this study, we demonstrated that TSAIII exerted a significant inhibitory effect on the distribution of cytoskeletal F-actin and cytoskeletal-related proteins, which contributed to the suppression of cell migration and invasion, without inhibiting cell growth or apoptosis. In the synergistic inhibitory analysis, cotreatment of TSAIII with αVβ3 integrin inhibitor [Cyclo(RGDyK)] or focal adhesion kinase (FAK) inhibitor (PF-573228) exerted greater synergistic inhibitory effects on the expression of Intergin αVβ3/FAK/cofilin axis, thus inhibiting the migration and invasion capacities of human osteosarcoma cells. TSAIII was demonstrated to significantly inhibit the pulmonary metastasis formation of human osteosarcoma cells in vivo in metastasis animal models. These findings reveal the inhibitory effects of TSAIII on the metastasis progression of human osteosarcoma cells and the regulation of integrin-αVβ3-FAK-Src and TESK1/p-cofilin mediated cytoskeletal F-actin pathway. Therefore, TSAIII might represent a novel strategy for the auxiliary treatment of human osteosarcoma cells.

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LncRNA GAS5 suppresses the proliferation and invasion of osteosarcoma cells via the miR-23a-3p/PTEN/PI3K/AKT pathway

10.21203/rs.3.rs-26945/v2 ◽

2020 ◽

Author(s):

Jianmin Liu ◽

Ming Chen ◽

Longyang Ma ◽

Xingbo Dang ◽

Gongliang Du

Keyword(s):

Tumor Suppressor ◽

Tumor Growth ◽

Akt Pathway ◽

Osteosarcoma Cell ◽

Osteosarcoma Cells ◽

Cell Behaviors ◽

Human Osteosarcoma ◽

Proliferation And Invasion

Abstract Background: Accumulating evidence has shown that lncRNA growth arrest special 5 (GAS5) is a well‑known tumor suppressor in the pathogenesis of a variety of human cancers. However, the detailed role of GAS5 in osteosarcoma is largely unclear. Here, we explore the role of GAS5 in progression of osteosarcoma. Methods: The expression level of GAS5 was detected in human osteosarcoma tissues and matched adjacent tissues, as well as osteosarcoma cell lines and non-malignant osteoblast cells. Then, in vitro gain- and loss-of-function experiments, with the pcDNA-GAS5 expression vector and GAS5-siRNA, were performed in U2OS and HOS cells to determine the effect of GAS5 on osteosarcoma cell proliferation and invasion. Subsequently, we searched potential miRNA targets with bioinformatics analysis and confirmed their interaction by using luciferase reporter gene and RNA pull-down assays. The function and mechanism of miR-23a-3p in proliferation and invasion was also investigated in U2OS and HOS cells. Furthermore, rescue experiments were performed to verify the involvement of miR-23a-3p and its target gene in GAS5-mediated cell behaviors. Finally, a xenograft nude mouse model was established by subcutaneous injection with U2OS cells overexpressing GAS5 or not, and the effect of GAS5 on tumor growth in vivo was evaluated. Results: GAS5 was downregulated in human osteosarcoma tissues and cell lines. Overexpression of GAS5 could significantly suppress, and downregulation of GAS5 promoted, proliferation and invasion of osteosarcoma cells. GAS5 could directly bind with and downregulated miR-23a-3p that post-transcriptionally downregulated the tumor suppressor PTEN and positively regulated proliferation and invasion of osteosarcoma cells. Rescue experiments confirmed the involvement of miR-23a-3p and PTEN in GAS5-mediated cell behaviors by modifying the phosphatidylinositol-3-kinases/protein-serine-threonine kinase (PI3K/AKT) pathway. GAS5 could inhibit tumor growth in vivo . Conclusion: GAS5 functions as a competing endogenous RNA , sponging miR-23a-3p, to promote PTEN expression and suppress cell growth and invasion in osteosarcoma by regulating the PI3K/AKT pathway.

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PTEN loss activates a functional AKT/CXCR4 signaling axis to potentiate tumor growth and lung metastasis in human osteosarcoma cells

Clinical & Experimental Metastasis ◽

10.1007/s10585-019-09998-7 ◽

2019 ◽

Vol 37 (1) ◽

pp. 173-185 ◽

Cited By ~ 6

Author(s):

Yongming Xi ◽

Zonghua Qi ◽

Jinfeng Ma ◽

Yan Chen

Keyword(s):

Tumor Growth ◽

Lung Metastasis ◽

Osteosarcoma Cells ◽

Pten Loss ◽

Cxcr4 Signaling ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

Signaling Axis

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Nucleophosmin Is a Binding Partner of Nucleostemin in Human Osteosarcoma Cells

Molecular Biology of the Cell ◽

10.1091/mbc.e08-02-0128 ◽

2008 ◽

Vol 19 (7) ◽

pp. 2870-2875 ◽

Cited By ~ 16

Author(s):

Hanhui Ma ◽

Thoru Pederson

Keyword(s):

Cell Cycle ◽

Cell Cycle Progression ◽

Embryonic Stem ◽

Bimolecular Fluorescence Complementation ◽

Osteosarcoma Cells ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

Cell Cycle Regulatory Proteins ◽

High Degree

Nucleostemin (NS) is expressed in the nucleoli of adult and embryonic stem cells and in many tumors and tumor-derived cell lines. In coimmunoprecipitation experiments, nucleostemin is recovered with the tumor suppressor p53, and more recently we have demonstrated that nucleostemin exerts its role in cell cycle progression via a p53-dependent pathway. Here, we report that in human osteosarcoma cells, nucleostemin interacts with nucleophosmin, a nucleolar protein believed to possess oncogenic potential. Nucleostemin (NS) and nucleophosmin (NPM) displayed an extremely high degree of colocalization in the granular component of the nucleolus during interphase, and both proteins associated with prenucleolar bodies in late mitosis before the reformation of nucleoli. Coimmunoprecipitation experiments revealed that NS and NPM co-reside in complexes, and yeast two-hybrid experiments confirmed that they are interactive proteins, revealing the NPM-interactive region to be the 46-amino acid N-terminal domain of NS. In bimolecular fluorescence complementation studies, bright nucleolar signals were observed, indicating that these two proteins directly interact in the nucleolus in vivo. These results support the notion that cell cycle regulatory proteins congress and interact in the nucleolus, adding to the emerging concept that this nuclear domain has functions beyond ribosome production.

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Monitoring of Xenograft Tumor Growth and Response to Chemotherapy by Non-Invasive In Vivo Multispectral Fluorescence Imaging

PLoS ONE ◽

10.1371/journal.pone.0047927 ◽

2012 ◽

Vol 7 (10) ◽

pp. e47927 ◽

Cited By ~ 16

Author(s):

Henrike Caysa ◽

Stefan Hoffmann ◽

Jana Luetzkendorf ◽

Lutz Peter Mueller ◽

Susanne Unverzagt ◽

...

Keyword(s):

Tumor Growth ◽

Fluorescence Imaging ◽

Xenograft Tumor ◽

Non Invasive ◽

Response To Chemotherapy ◽

Xenograft Tumor Growth ◽

Multispectral Fluorescence Imaging

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Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo

Cell Death and Disease ◽

10.1038/cddis.2016.138 ◽

2016 ◽

Vol 7 (6) ◽

pp. e2247-e2247 ◽

Cited By ~ 75

Author(s):

H Wang ◽

T Zhang ◽

W Sun ◽

Z Wang ◽

D Zuo ◽

...

Keyword(s):

Signaling Pathway ◽

Osteosarcoma Cells ◽

Jnk Signaling ◽

Human Osteosarcoma ◽

Phase Arrest ◽

Human Osteosarcoma Cells ◽

M Phase ◽

Jnk Signaling Pathway

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Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

Cell Death and Disease ◽

10.1038/cddis.2017.488 ◽

2017 ◽

Vol 8 (10) ◽

pp. e3113-e3113 ◽

Cited By ~ 38

Author(s):

Jian Zhu ◽

Wei Yu ◽

Bing Liu ◽

Yitian Wang ◽

Jianlin shao ◽

...

Keyword(s):

P38 Mapk ◽

Signalling Pathway ◽

Osteosarcoma Cells ◽

Mapk Signalling Pathway ◽

Human Osteosarcoma ◽

Human Osteosarcoma Cells ◽

Mapk Signalling

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SECRETION OF A BONE-INDUCING AGENT (BIA) BY CULTURED SAOS-2 HUMAN OSTEOSARCOMA CELLS

Journal of Musculoskeletal Research ◽

10.1142/s0218957799000063 ◽

1999 ◽

Vol 03 (01) ◽

pp. 39-48 ◽

Cited By ~ 4

Author(s):

H. C. Anderson ◽

D. J. Gurley ◽

H. H. T. Hsu ◽

X. M. Aguilera ◽

L. S. Davis ◽

...

Keyword(s):

Conditioned Medium ◽

Culture Medium ◽

Osteosarcoma Cells ◽

Western Blots ◽

Serum Free ◽

Human Osteosarcoma ◽

Cell Extracts ◽

Human Osteosarcoma Cells ◽

Freeze Dried

An extractable bone-inducing agent has recently been identified in freeze-dried preparations of Saos-2 cultured human osteosarcoma cells. Although not all osteoinductive components of Saos-2 cell extracts have been identified, we have shown that Saos-2 cells express high levels of mRNA for bone morphogenetic proteins (BMPs)-1,2,3,4 and 6. Any or all of these BMPs (plus possible unknown factors) may be involved in ectopic bone induction, and may act as paracrine agents, conveying morphogenetic information to juxtaposed osteoprogenitor cells. Our objectives in this study were: 1) to determine whether Saos-2 cells secrete BIA into their culture medium; and 2) if secreted, to determine whether released bone-inducing agent is soluble and/or particulate and contains BMPs. Saos-2 cells were grown to confluence, and then overlaid with serum-free DMEM culture medium for 48 hours. The serum-free conditioned medium was then decanted and filtered through 0.45μ pore-size filters to retain any vesicles or other particulates released by the cells. Particulate protein retained on the 0.45μ filter (designated "retentate") was extracted into 6M urea and bioassayed for bone-inducing activity in Nu/Nu mice, along with soluble media protein that had passed through the 0.45μ filter (designated "filtrate") plus freeze-dried Saos-2 cells from which conditioned the culture medium was obtained. Results indicate that the bone-inducing agent of Saos-2 cells is not only retained by the cells, but is also secreted in both soluble and particulate forms into serum-free conditioned medium. Bone-inducing activity (per mg protein) is more concentrated in the particulate fraction, which is shown by electron microscopy to contain a mixture of vesicles (similar to matrix vesicles) plus electron dense granules (resembling ribosomes) and 10 mM microfilaments (of possible collagenous or cytoskeletal origin). BMP-1,2,3,4,6 and 7 were detected by western blots in both the soluble and particulate fractions of conditioned medium. Thus, it is indicated that Saos-2 cells secrete an osteoinductive factor which may function in vivo as a paracrine morphogenetic agent.

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