Inhibitory effect of aminoethyl-chitooligosaccharides on invasion of human fibrosarcoma cells

2016 ◽  
Vol 45 ◽  
pp. 309-314 ◽  
Author(s):  
Sugyeong Hong ◽  
Dai-Nghiep Ngo ◽  
Moon-Moo Kim
Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 604
Author(s):  
Hojun Kim ◽  
Fatih Karadeniz ◽  
Chang-Suk Kong ◽  
Youngwan Seo

The current study investigated the ability of two secoiridoids, GL-3 (1) and oleonuezhenide (2), isolated from the fruits of Ligustrum japonicum to inhibit MMP-2 and -9 activity in phorbol 12-myristate 13-acetate (PMA)-induced HT-1080 human fibrosarcoma cells. Both compounds 1 and 2 were able to exert lowered gelatin digestion activity for MMP-2 and -9 tested by gelatin zymography via suppressing the release of MMPs to culture medium according to ELISA results. Treatment with compounds was also able to suppress the expression of both mRNA and protein levels of MMP-2 and -9. Action mechanism behind the MMP inhibitory effect of the compounds was suggested to be via MAPK pathway indicated by decreased levels of phosphorylated p38, ERK and JNK proteins evaluated employing immunoblotting. Compound 1 was shown to be slightly more active to inhibit MMP-2 and -9, however, compound 2 showed more regular dose-dependency during inhibition. In conclusion, this study suggested that GL-3 and oleonuezhenide were notable natural origin potent MMP inhibitors and could serve as lead compounds for development of anti-invasive MMP inhibitors against tumor metastasis.


2020 ◽  
Vol 13 ◽  
Author(s):  
Jaeryeon Kim ◽  
Moon-Moo Kim

Background: Anti-cancer effect of lapachol contained in Tabebuia avellandae has been poorly understood until now. Objective: The aim of this study was to investigate the inhibitory effect of lapachol on MMPs related to cell invasion. Its action mechanism was elucidated by analyzing the activity and the expression of MMPs and the proteins involved in the signalling pathway of cell invasion. Methods: The cytotoxicity of lapachol was evaluated by MTT assay in HT1080 cells. The effects of lapachol on the expression and the activation of MMPs were analyzed by western blot, immunofluorescence staining and gelatin zymography assays. Their gene expression was analyzed by RT-PCR, and metastasis was evaluated by cell invasion assay. Results: Lapachol below 2 µM showed no cytotoxicity. It was observed that lapachol above 0.5 µM inhibited the activation of MMP-2 and MMP-9 stimulated by PMA. In particular, the protein and gene expression levels of MMP-2 stimulated by PMA were remarkably decreased in the presence of lapachol at 1 µM compared with PMA treatment group. In addition, lapachol increased the expression level of TIMP-1 compared with PMA treatment group. Moreover, lapachol decreased the expression level of p-p38 among MAPKs compared with PMA treatment group. It was also found that the expression level of p65, a part of NF-kB, in nuclei was reduced in the presence of lapachol above 0.5 µM compared with PMA treatment group. In addition, lapachol inhibited the invasion of human fibrosarcoma cells stimulated with VEGF. Conclusion: Above results suggest that lapachol could play an important role in the modulation of MMPs related to cell invasion via the increase of TIMP-1 expression as well as the inactivation of p38 through NF-kB transcription factor.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryo Saga ◽  
Yusuke Matsuya ◽  
Rei Takahashi ◽  
Kazuki Hasegawa ◽  
Hiroyuki Date ◽  
...  

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.


Sarcoma ◽  
2001 ◽  
Vol 5 (4) ◽  
pp. 197-202 ◽  
Author(s):  
Mitsunori Kaya ◽  
Takuro Wada ◽  
Satoshi Nagoya ◽  
Satoshi Kawaguchi ◽  
Toshihiko Yamashita ◽  
...  

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.


1982 ◽  
Vol 203 (1) ◽  
pp. 235-238 ◽  
Author(s):  
K C Ramage ◽  
J H J Dunn ◽  
A M Campbell

A chromosomal protein antigen specific for human granulocytes is described. The antigen is present in large amounts in granulocytes and in granulocytic leukaemia. It is absent from HeLa cells, human fibrosarcoma cells and human lymphocytes. It is, however, present in small amounts in other human haemopoietic cell lines. The antigen binds tightly to DNA and requires the presence of DNA to react with the antibody.


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