scholarly journals 4-Methylumbelliferone administration enhances radiosensitivity of human fibrosarcoma by intercellular communication

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryo Saga ◽  
Yusuke Matsuya ◽  
Rei Takahashi ◽  
Kazuki Hasegawa ◽  
Hiroyuki Date ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Dose Range ◽  
Synthesis Inhibitor ◽  
X Ray ◽  
Tumour Control ◽  
Synergetic Effects ◽  
Fibrosarcoma Cells ◽  
Oxidative Stress Level ◽  
Human Fibrosarcoma Cells

AbstractHyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.

scholarly journals 4-Methylumbelliferone Administration Enhances Radiosensitivity of Human Fibrosarcoma by Intercellular Communication

2021 ◽  
Author(s):  
Ryo Saga ◽  
Yusuke Matsuya ◽  
Rei Takahashi ◽  
Kazuki Hasegawa ◽  
Hiroyuki Date ◽  
...  
Keyword(s):  
Intercellular Communication ◽  
Dose Range ◽  
Synthesis Inhibitor ◽  
X Ray ◽  
Tumour Control ◽  
Synergetic Effects ◽  
Fibrosarcoma Cells ◽  
Oxidative Stress Level ◽  
Human Fibrosarcoma Cells

Abstract Hyaluronan synthesis inhibitor 4-methylumbelliferone (4-MU) is a candidate of radiosensitizers which enables both anti-tumour and anti-metastasis effects in X-ray therapy. The curative effects under such 4-MU administration have been investigated in vitro; however, the radiosensitizing mechanisms remain unclear. Here, we investigated the radiosensitizing effects under 4-MU treatment from cell experiments and model estimations. We generated experimental surviving fractions of human fibrosarcoma cells (HT1080) after 4-MU treatment combined with X-ray irradiation. Meanwhilst, we also modelled the pharmacological effects of 4-MU treatment and theoretically analyzed the synergetic effects between 4-MU treatment and X-ray irradiation. The results show that the enhancement of cell killing by 4-MU treatment is the greatest in the intermediate dose range of around 4 Gy, which can be reproduced by considering intercellular communication (so called non-targeted effects) through the model analysis. As supposed to be the involvement of intercellular communication in radiosensitization, the oxidative stress level associated with reactive oxygen species (ROS), which leads to DNA damage induction, is significantly higher by the combination of 4-MU treatment and irradiation than only by X-ray irradiation, and the radiosensitization by 4-MU can be suppressed by the ROS inhibitors. These findings suggest that the synergetic effects between 4-MU treatment and irradiation are predominantly attributed to intercellular communication and provide more efficient tumour control than conventional X-ray therapy.

scholarly journals TNP-470 Suppresses the Tumorigenicity of HT1080 Fibrosarcoma Tumor Through the Inhibition of VEGF Secretion From the Tumor Cells

Sarcoma ◽  
2001 ◽  
Vol 5 (4) ◽  
pp. 197-202 ◽  
Author(s):  
Mitsunori Kaya ◽  
Takuro Wada ◽  
Satoshi Nagoya ◽  
Satoshi Kawaguchi ◽  
Toshihiko Yamashita ◽  
...  
Keyword(s):  
Conditioned Medium ◽  
Direct Action ◽  
Angiogenesis Inhibitor ◽  
Angiogenesis Inhibitors ◽  
Fibrosarcoma Cells ◽  
Ht1080 Cells ◽  
Human Fibrosarcoma Cells ◽  
And Migration

Angiogenesis inhibitors are a novel class of promising therapeutic agents for treating cancer. TNP-470, a systemic analogue of fumagillin, is an angiogenesis inhibitor capable of suppressing the tumorigenicity in several animal models even though the mechanisms of action have not been completely clarified. In the current study, we investigated the effects of TNP-470 on human fibrosarcoma cellsin vivoandin vitro. The administration of TNP-470 could suppress the tumorigenicity of HT1080 fibrosarcoma tumor. The conditioned medium from HT1080 fibrosarcoma cells treated with TNP-470 inhibited the proliferation and migration of human endothelial cell line, HUVEC and ECV304. The concentration of VEGF in the conditioned medium from HT1080 cells treated with TNP-470 was lower than that of the cells without TNP-470 treatment, indicating that TNP-470 downregulates the secretion of VEGF from HT1080 cells. These findings strongly suggest that the direct action of TNP-470 on sarcoma cells inhibits angiogenesis through the downregulation of VEGF secretion and this angiogenesis suppression resulted in the inhibition of tumorigenicity of HT1080 fibrosarcoma tumo.

scholarly journals The Effect of Hydroxybenzoate Lithium Complexes in Inducing Apoptosis in HT-1080 Human Fibrosarcoma Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Jassem G. Mahdi ◽  
Eamon J. Mahdi ◽  
Amal Al-Hazzaa ◽  
Chris J. Pepper
Keyword(s):  
Biological Activities ◽  
Cytotoxic Activities ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Beneficial Effects ◽  
Fibrosarcoma Cells ◽  
Lithium Complexes ◽  
Human Fibrosarcoma Cells ◽  
Apoptotic Effects

There has been a growing interest in the beneficial effects of simple phenolic acids and their ability to exhibit various biological activities. The aim of this study was to assess in vitro biological activities of 2-, 3-, and 4-hydroxybenzoate lithium (HBLi) complexes on HT-1080 human fibrosarcoma cells by methods of using a metabolic activity assay, immunochemical and morphological techniques. Results showed that HBLi complexes exert their cytotoxic activities in a concentration- and chemical structure-dependent manner in the following order: 4-HBLi > 3-HBLi > 2-HBLi. Flow cytometry displayed evidence of apoptosis induced by 3-HBLi (21.8%) and 4-HBLi (33.2%). These results were verified by SEM, which revealed the formation of apoptotic bodies. In addition, these 3-HBLi and 4-HBLi caused an increase in HT-1080 cell cycle arrest in G0/G1 phase when compared to the controls (25% and 30.6%, resp.) when cells were treated with 6 mM for 24 hours. Immunochemical studies related to the molecular mechanism of apoptosis indicated that HBLi complexes downregulated the expression of Bcl-2 and upregulated Bax, p53, and caspases-3 in a concentration-dependent manner. HBLi complexes lowered Bcl-2/Bax ratios and induced the expression of p53 and caspase-3. These results suggest that HBLi complexes may exert their apoptotic effects through mitochondrial-mediated, caspase-dependent, apoptotic mechanisms.

Solvent-partitioned fractions from Ishige okamurae extract inhibit MMP-2 and MMP-9 activities in human fibrosarcoma cells in vitro

2017 ◽  
Vol 30 (1) ◽  
pp. 121-127
Author(s):  
Fatih Karadeniz ◽  
Seul-Gi Lee ◽  
Jung Hwan Oh ◽  
Ga Hyun Yu ◽  
Mi-Soon Jang ◽  
...  
Keyword(s):  
Ishige Okamurae ◽  
Fibrosarcoma Cells ◽  
Human Fibrosarcoma Cells

scholarly journals Stanniocalcin 1 and 2 are secreted as phosphoproteins from human fibrosarcoma cells

2000 ◽  
Vol 350 (2) ◽  
pp. 453-461 ◽  
Author(s):  
Derek A. JELLINEK ◽  
Andy C. CHANG ◽  
Martin R. LARSEN ◽  
Xin WANG ◽  
Phillip J. ROBINSON ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Mammalian Cells ◽  
Phosphorylation Site ◽  
Mrna Levels ◽  
Intact Cells ◽  
Fibrosarcoma Cells ◽  
Ht1080 Cells ◽  
Human Fibrosarcoma Cells

Stanniocalcin 1 (STC1) and stanniocalcin 2 (STC2) are two recently identified mammalian peptide hormones. STC1 plays a role in calcium and phosphate homoeostasis, while the role of STC2 is unknown. We examined a human fibrosarcoma cell line, HT1080, that has high steady-state STC1 and STC2 mRNA levels, to determine whether these proteins are secreted. Following incubation of HT1080 cells with 32P, labelled STC1 and STC2 were found to be secreted into the medium. STC1 was phosphorylated in vitro by protein kinase C (PKC). In vitro and in vivo phosphorylation both occurred exclusively on serine and the phosphopeptide maps were similar, suggesting that PKC might be the in vivo kinase. STC2 was phosphorylated in vitro by casein kinase II (CK2), in vitro and in vivo phosphorylation were exclusively on serine and the phosphopeptide maps were indistinguishable. Phosphorylation of STC2 in intact cells resulted from the action of an ecto-protein kinase, since exogenous STC2 was phosphorylated by HT1080 cells and no phosphorylated STC2 was detectable inside the cells. The ectokinase activity was abolished by heparin and GTP could substitute for ATP as the phosphate donor, indicative of an ecto-CK2-like activity. The in vitro CK2 phosphorylation site was shown by matrix-assisted laser-desorption ionization–time-of-flight MS to be a single serine located between Ser-285 and Ser-298 in the C-terminal region of STC2. This is the first report of the secretion of STC1 or STC2 from mammalian cells. We conclude that these human fibrosarcoma cells express both STC1 and STC2 as secreted phosphoproteins in vivo, with STC2 being phosphorylated by an ecto-CK2-like enzyme.

In Vivo and In Vitro Antitumor Effect of Ascorbic Acid, Lysine, Proline, Arginine, and Green Tea Extract on Human Fibrosarcoma Cells HT-1080

2006 ◽  
Vol 23 (1) ◽  
pp. 105-112 ◽  
Author(s):  
M. Waheed Roomi ◽  
Vadim Ivanov ◽  
Tatiana Kalinovsky ◽  
Aleksandra Niedzwiecki ◽  
Matthias Rath
Keyword(s):  
Ascorbic Acid ◽  
Green Tea ◽  
Antitumor Effect ◽  
Green Tea Extract ◽  
Fibrosarcoma Cells ◽  
Human Fibrosarcoma Cells ◽  
Tea Extract

scholarly journals Theoretical derivation and clinical dose-response quantification of a unified multi-activation (UMA) model of cell survival from a logistic equation

BJR|Open ◽  
2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Shidong Li
Keyword(s):  
Cell Survival ◽  
Normal Tissue ◽  
Dose Range ◽  
Normal Tissue Complication Probability ◽  
Order Reaction ◽  
Second Order Reaction ◽  
X Ray ◽  
Tumour Control ◽  
Tumour Control Probability ◽  
X Ray Imaging

Objective: To theoretically derive a unified multiactivation (UMA) model of cell survival after ionising radiation that can accurately assess doses and responses in radiotherapy and X-ray imaging. Methods: A unified formula with only two parameters in fitting of a cell survival curve (CSC) is first derived from an assumption that radiation-activated cell death pathways compose the first- and second-order reaction kinetics. A logit linear regression of CSC data is used for precise determination of the two model parameters. Intrinsic radiosensitivity, biologically effective dose (BED), equivalent dose to the traditional 2 Gy fractions (EQD2), tumour control probability, normal-tissue complication probability, BED50 and steepness (Γ50) at 50% of tumour control probability (or normal-tissue complication probability) are analytical functions of the model and treatment (or imaging) parameters. Results: The UMA model has almost perfectly fit typical CSCs over the entire dose range with R2≥0.99. Estimated quantities for stereotactic body radiotherapy of early stage lung cancer and the skin reactions from X-ray imaging agree with clinical results. Conclusion: The proposed UMA model has theoretically resolved the catastrophes of the zero slope at zero dose for multiple target model and the bending curve at high dose for the linear quadratic model. More importantly, it analytically predicts dose–responses to various dose–fraction schemes in radiotherapy and to low dose X-ray imaging based on these preclinical CSCs. Advances in knowledge: The discovery of a unified formula of CSC over the entire dose range may reveal a common mechanism of the first- and second-order reaction kinetics among multiple CD pathways activated by ionising radiation at various dose levels.

scholarly journals Cathepsin B-Cleavable Cyclopeptidic Chemotherapeutic Prodrugs

Molecules ◽  
2020 ◽  
Vol 25 (18) ◽  
pp. 4285
Author(s):  
Viktorija Herceg ◽  
Jordan Bouilloux ◽  
Karolina Janikowska ◽  
Eric Allémann ◽  
Norbert Lange
Keyword(s):  
Cathepsin B ◽  
Cell Membrane Permeability ◽  
Cycle Arrest ◽  
Fibrosarcoma Cells ◽  
A Cell ◽  
Upper Face ◽  
G2 Phase ◽  
Human Fibrosarcoma Cells ◽  
Targeted Release

Cyclopeptidic chemotherapeutic prodrugs (cPCPs) are macromolecular protease-sensitive doxorubicin (DOX) prodrugs synthesized from a cyclodecapeptidic scaffold, termed Regioselectively Addressable Functionalized Template (RAFT). In order to increase the chemotherapeutic potential of DOX and limit its toxicity, we used a Cathepsin B (Cat B)-sensitive prodrug concept for its targeted release since this enzyme is frequently overexpressed in cancer cells. Copper-free “click” chemistry was used to synthesize cPCPs containing up to four DOX moieties tethered to the upper face of the scaffold through a Cat B-cleavable peptidic linker (GAGRRAAG). On the lower part, PEG 5, 10 and 20 kDa and a fifth peptidyl DOX moiety were grafted in order to improve the solubility, bioavailability and pharmacokinetic profiles of the compound. In vitro results on HT1080 human fibrosarcoma cells showed that cPCPs display a delayed action that consists of a cell cycle arrest in the G2 phase comparable to DOX alone, and increased cell membrane permeability.

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