scholarly journals 4-Hydroxy-2-nonenal Induces Apoptosis by Inhibiting AKT Signaling in Human Osteosarcoma Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Guang-rong Ji ◽  
Nai-chun Yu ◽  
Xiang Xue ◽  
Zong-guang Li
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Cell Death ◽  
Osteosarcoma Cells ◽  
Physiochemical Properties ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
The Status ◽  
Bodies Of Evidence

The onset of lipid peroxidation within cellular membranes is associated with changes in their physiochemical properties and enzymatic dysfunction of the membrane environment. There are increasing bodies of evidence indicating that aldehydic molecules generated endogenously during the process of lipid peroxidation are causally involved in most of the pathophysiological effects associated with oxidative stress in cells and tissues. 4-Hydroxy-2-nonenal (4-HNE), among them, is believed to be largely responsible for cytopathological effects observed during oxidative stressin vivoand has achieved the status of one of the best recognized and most studied of the cytotoxic products of lipid peroxidation. Here, we reported that 4-HNE treatment may induce cell death in MG63 human osteosarcoma cells. The 4-HNE treatment could activate caspase-3 and alter the Bax/Bcl-2 apoptotic signaling. All these changes are due to the inhibition of AKT activity by 4-HNE treatment, and we also found that the p70S6K activity, downstream factors of AKT, was also blocked by 4-HNE. Our results revealed the molecular mechanism of how 4-HNE induces cell death in MG63 human osteosarcoma cells, which contributes to the clinical treatment of cancer therapy.

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 Potential Antimetastatic Effect of Timosaponin AIII against Human Osteosarcoma Cells through Regulating the Integrin/FAK/Cofilin Axis

2021 ◽  
Vol 14 (3) ◽  
pp. 260
Author(s):  
Yi-Hsien Hsieh ◽  
Wen-Hung Hsu ◽  
Shun-Fa Yang ◽  
Chung-Jung Liu ◽  
Ko-Hsiu Lu ◽  
...  
Keyword(s):  
Integrin Αvβ3 ◽  
Migration And Invasion ◽  
Steroidal Saponin ◽  
Αvβ3 Integrin ◽  
Osteosarcoma Cells ◽  
Inhibitory Effects ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells ◽  
Timosaponin Aiii

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.

Ketoconazole-induced JNK phosphorylation and subsequent cell death via apoptosis in human osteosarcoma cells

2009 ◽  
Vol 23 (7) ◽  
pp. 1268-1276 ◽  
Author(s):  
Ko-Long Lin ◽  
Chorng-Chih Huang ◽  
Jin-Shiung Cheng ◽  
Jeng-Yu Tsai ◽  
Yih-Chau Lu ◽  
...  
Keyword(s):  
Cell Death ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

scholarly journals Nucleophosmin Is a Binding Partner of Nucleostemin in Human Osteosarcoma Cells

2008 ◽  
Vol 19 (7) ◽  
pp. 2870-2875 ◽  
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.

scholarly journals Decoding the anticancer activity of VO-clioquinol compound: the mechanism of action and cell death pathways in human osteosarcoma cells

Metallomics ◽  
2017 ◽  
Vol 9 (7) ◽  
pp. 891-901 ◽  
Author(s):  
Ignacio E. León ◽  
Paula Díez ◽  
Enrique J. Baran ◽  
Susana B. Etcheverry ◽  
Manuel Fuentes
Keyword(s):  
Cell Death ◽  
Anticancer Drugs ◽  
Mechanism Of Action ◽  
Platinum Metal ◽  
Osteosarcoma Cells ◽  
Vanadium Compounds ◽  
New Class ◽  
Human Osteosarcoma ◽  
Cell Death Pathways ◽  
Human Osteosarcoma Cells

Vanadium compounds were studied in recent years by considering them as a representative of a new class of non-platinum metal anticancer drugs.

scholarly journals The plant alkaloid voacamine induces apoptosis-independent autophagic cell death on both sensitive and multidrug resistant human osteosarcoma cells

Autophagy ◽  
2008 ◽  
Vol 4 (8) ◽  
pp. 1020-1033 ◽  
Author(s):  
Stefania Meschini ◽  
Maria Condello ◽  
Annarica Calcabrini ◽  
Manuela Marra ◽  
Giuseppe Formisano ◽  
...  
Keyword(s):  
Cell Death ◽  
Multidrug Resistant ◽  
Autophagic Cell Death ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells

Hyperthermia enhances the effect of β-lapachone to cause γH2AX formations and cell death in human osteosarcoma cells

2010 ◽  
Vol 27 (1) ◽  
pp. 53-62 ◽  
Author(s):  
Takeshi Hori ◽  
Takashi Kondo ◽  
Hyemi Lee ◽  
Chang W. Song ◽  
Heon Joo Park
Keyword(s):  
Cell Death ◽  
Osteosarcoma Cells ◽  
Human Osteosarcoma ◽  
Human Osteosarcoma Cells
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