scholarly journals Combined bezafibrate, medroxyprogesterone acetate and valproic acid treatment inhibits osteosarcoma cell growth without adversely affecting normal mesenchymal stem cells

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Jonathan J. Sheard ◽  
Andrew D. Southam ◽  
Hannah L. MacKay ◽  
Max A. Ellington ◽  
Martyn D. Snow ◽  
...  
Keyword(s):  
Valproic Acid ◽  
Cell Growth ◽  
Medroxyprogesterone Acetate ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Growth And Survival ◽  
Human Osteosarcoma ◽  
Cell Extracts ◽  
Human Osteosarcoma Cells ◽  
Mg63 Cells

Abstract Drug repurposing is a cost-effective means of targeting new therapies for cancer. We have examined the effects of the repurposed drugs, bezafibrate, medroxyprogesterone acetate and valproic acid on human osteosarcoma cells, i.e., SAOS2 and MG63 compared with their normal cell counterparts, i.e. mesenchymal stem/stromal cells (MSCs). Cell growth, viability and migration were measured by biochemical assay and live cell imaging, whilst levels of lipid-synthesising enzymes were measured by immunoblotting cell extracts. These drug treatments inhibited the growth and survival of SAOS2 and MG63 cells most effectively when used in combination (termed V-BAP). In contrast, V-BAP treated MSCs remained viable with only moderately reduced cell proliferation. V-BAP treatment also inhibited migratory cell phenotypes. MG63 and SAOS2 cells expressed much greater levels of fatty acid synthase and stearoyl CoA desaturase 1 than MSCs, but these elevated enzyme levels significantly decreased in the V-BAP treated osteosarcoma cells prior to cell death. Hence, we have identified a repurposed drug combination that selectively inhibits the growth and survival of human osteosarcoma cells in association with altered lipid metabolism without adversely affecting their non-transformed cell counterparts.

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).

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

1999 ◽  
Vol 03 (01) ◽  
pp. 39-48 ◽  
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.

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.

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