Fucoidan suppresses the gastric cancer cell malignant phenotype and production of TGF-β1 via CLEC-2

Glycobiology ◽  
2019 ◽  
Vol 30 (5) ◽  
pp. 301-311 ◽  
Author(s):  
Ling Xu ◽  
Fenglin Liu ◽  
Can Li ◽  
Shuxuan Li ◽  
Hao Wu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Transcription Factor ◽  
Gastric Carcinoma ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inhibitory Effect ◽  
Sulfated Polysaccharide ◽  
Migration And Invasion ◽  
Malignant Phenotype ◽  
Tgf Β1

Abstract The sulfated polysaccharide fucoidan displays excellent anticancer properties with low toxicity in many kinds of cancers. However, its detailed pharmacological effect and mechanism of action in gastric carcinoma remains unclear. In this study, we found that fucoidan could suppress gastric cancer (GC) cell growth, as well as cell migration and invasion. A cytokine expression screen demonstrated that transforming growth factor beta 1 (TGF-β1) secretion was decreased in fucoidan-treated cells. Fucoidan has been reported to be a platelet agonist for the C-type lectin-like receptor 2 (CLEC-2), and our previous research found that upregulation of CLEC-2 inhibited GC progression. Here, we confirmed that fucoidan, combined with CLEC-2, significantly increased CLEC-2 expression in GC cells via the transcription factor caudal type homeobox transcription factor 2, an important regulator of gut homeostasis. In addition, the inhibitory effect of fucoidan on the GC cell malignant phenotype and TGF-β1 secretion could be restored by knocking down CLEC-2. Thus, our data suggest that fucoidan targets CLEC-2 to exert antitumorigenesis and antimetastatic activity, suggesting that fucoidan is a promising treatment for gastric carcinoma.

Transforming Growth Factor Beta 1 Affects Gastric Cancer Cell Proliferation, Migration, and Invasion by Regulating Phosphatase and Tensin Homolog

2021 ◽  
Vol 11 (4) ◽  
pp. 731-735
Author(s):  
Yuchen Wang ◽  
Zhimin Huang
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cell Migration ◽  
Cancer Cell ◽  
Transforming Growth Factor Beta ◽  
Gastric Cancer Cell ◽  
Transforming Growth Factor ◽  
Migration And Invasion ◽  
Control Group ◽  
Tgf Β1

Gastric cancer (GC) is a common tumor with high incidence and poor prognosis. So far, the pathogenesis of GC has not been fully elucidated, which has brought great difficulty to the treatment. TGF-β regulates cell growth and differentiation. As a key member, TGF-β1 is abnormally expressed in various tumors, but its role on GC and related mechanisms have not been elucidated. Gastric cancer and adjacent tissues were collected to measure TGF-β1 level by real-time PCR. SGC-7901 cell was assigned into control group, mock group, and TGF-β1 siRNA group followed by analysis of TGF-β1 level by ELISA, cell proliferation by MTT assay, apoptosis by flow cytometry, cell migration by cell scratch test, cell invasion by Transwell chamber assay, and Bcl-2, Bax, and PTEN level by Western blot. TGF-β1 was significantly upregulated in GC tissues (P <0.05) and increased with TNM stage dependence. TGF-β1 siRNA transfection significantly decreased TGF-β1 mRNA level and secretion, inhibited cell proliferation, increased apoptosis rate, and attenuated cell migration and invasion along with downregulated Bcl-2 and elevated Bax and PTEN expression (P <0.05). Downregulation of TGF-β1 can promote gastric cancer cell apoptosis, inhibit proliferation, migration, and invasion by regulating PTEN.

scholarly journals LY2157299 Monohydrate, a TGF-βR1 Inhibitor, Suppresses Tumor Growth and Ascites Development in Ovarian Cancer

Cancers ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 260 ◽  
Author(s):  
Qing Zhang ◽  
Xiaonan Hou ◽  
Bradley Evans ◽  
Jamison VanBlaricom ◽  
Saravut Weroha ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Cell Lines ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Migration And Invasion ◽  
Ascites Formation ◽  
Tgf Β1

Transforming growth factor beta (TGF-β) signaling has pleiotropic functions regulating cancer initiation, development, and metastasis, and also plays important roles in the interaction between stromal and cancer cells, making the pathway a potential therapeutic target. LY2157299 monohydrate (LY), an inhibitor of TGF-β receptor I (TGFBRI), was examined for its ability to inhibit ovarian cancer (OC) growth both in high-grade serous ovarian cancer (HGSOC) cell lines and xenograft models. Immunohistochemistry, qRT-PCR, and Western blot were performed to study the effect of LY treatment on expression of cancer- and fibroblast-derived genes. Results showed that exposure to TGF-β1 induced phosphorylation of SMAD2 and SMAD3 in all tested OC cell lines, but this induction was suppressed by pretreatment with LY. LY alone inhibited the proliferation, migration, and invasion of HGSOC cells in vitro. TGF-β1-induced fibroblast activation was blocked by LY. LY also delayed tumor growth and suppressed ascites formation in vivo. In addition, independent of tumor inhibition, LY reduces ascites formation in vivo. Using OVCAR8 xenograft specimens we confirmed the inhibitory effect of LY on TGF-β signaling and tumor stromal expression of collagen type XI chain 1 (COL11A1) and versican (VCAN). These observations suggest a role for anti-TGF-β signaling-directed therapy in ovarian cancer.

scholarly journals TGFβ1-induced cell motility is mediated through Cten in colorectal cancer

2018 ◽  
Author(s):  
Abdulaziz Asiri ◽  
Teresa Pereira Raposo ◽  
Abdulaziz Alfahed ◽  
Mohammad Ilyas
Keyword(s):  
Colorectal Cancer ◽  
Cell Motility ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Migration And Invasion ◽  
Mesenchymal Transition ◽  
Growth Factor Beta ◽  
Emt Markers ◽  
Tgf Β1

ABSTRACTCten is a tensin which promotes epithelial-mesenchymal transition (EMT) and cell motility. The precise mechanisms regulating Cten are unknown, although Cten could be regulated by several cytokines and growth factors. Since Transforming growth factor beta 1 (TGF-β1) regulates integrin function and promotes EMT / cell motility, we investigated whether this happens through Cten signalling in colorectal cancer (CRC).TGF-β1 signalling was modulated by either stimulation or knockdown in the CRC cell lines SW620 and HCT116. The effect of this modulation on expression of Cten, EMT markers and cellular function was tested. Cten role as a direct mediator of TGF-β1 signalling was investigated in a CRC cell line with a deleted Cten gene (SW620ΔCten).When TGF-β1 was stimulated or inhibited, this resulted in, respectively, upregulation and downregulation of Cten expression and EMT markers. Cell migration and invasion were significantly increased following TGF-β1 stimulation and lost by TGF-β1 knockdown. TGF-β1 stimulation in SW620ΔCten resulted in selective loss of the effect of TGF-β1 signalling on EMT and cell motility whilst the stimulatory effect on cell proliferation was retained.These data suggested Cten may play an essential role in mediating TGF-β1-induced EMT and cell motility and may play a role in metastasis in CRC.

scholarly journals Transcription Factor CTCFL Promotes cell Proliferation, Migration and Invasion in Gastric Cancer Via Activating DPPA2

2020 ◽  
Author(s):  
Haibo Yao ◽  
Qinshu Shao ◽  
Yanfei Shao
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Transcription Factor ◽  
Inhibitory Effect ◽  
Migration And Invasion ◽  
Gastric Cancer Cells ◽  
Positive Role ◽  
Promote Cell Proliferation ◽  
Transwell Invasion Assay

Abstract Background: The purpose of this study was to explore the relationship between CTCFL and DPPA2, and validate the positive role of CTCFL/DPPA2 in cell proliferation, migration and invasion in gastric cancer.Methods: Bioinformatics methods were applied for the prediction of gastric cancer-related transcription factors and corresponding target mRNAs. qRT-PCR and western blot were performed to test the levels of CTCFL and DPPA2. Then a series of in vitro experiments were conducted to assay the cell biological behaviors, including CCK-8, colony formation assay, wound healing assay and Transwell invasion assay. CHIP was carried out for assessment of the targeted relationship between CTCFL and DPPA2.Results: CTCFL and DPPA2 were both highly expressed in gastric cancer cells, and high CTCFLL and DPPA2 could promote cell proliferation, migration and invasion. CHIP validated that DPPA2 was a target of CTCFL. In addition, high DPPA2 could reverse the inhibitory effect of CTCFL silencing on the cell proliferation, migration and invasion in gastric cancer.Conclusion: The transcription factor CTCFL promotes cell proliferation, migration and invasion in gastric cancer via activating DPPA2.

scholarly journals Discovery of 9O-Substituted Palmatine Derivatives as a New Class of Anti-COL1A1 Agents Via Repressing TGF-β1/Smads and JAK1/STAT3 Pathways

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 773
Author(s):  
Tianyun Fan ◽  
Maoxu Ge ◽  
Zhihao Guo ◽  
Hongwei He ◽  
Na Zhang ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Inhibitory Effect ◽  
Mechanism Study ◽  
Protein Levels ◽  
New Class ◽  
Stat3 Signaling ◽  
Ic50 Value ◽  
Ld50 Value ◽  
Tgf Β1

Twenty 9O-substituted palmatine derivatives were prepared and tested for their biological effect against collagen α1 (I) (COL1A1) promotor in human hepatic stellate LX-2 cells. The structure−activity relationship (SAR) indicated that the introduction of a benzyl motif on the 9O atom was favorable for activity. Among them, compound 6c provided the highest inhibitory effect against COL1A1 with an IC50 value of 3.98 μM, and it also dose-dependently inhibited the expression of fibrogenic COL1A1, α-soomth muscle actin (α-SMA), matrix metalloprotein 2 (MMP2) in both mRNA and protein levels, indicating extensive inhibitory activity against fibrogenesis. A further primary mechanism study indicated that it might repress the hepatic fibrogenesis via inhibiting both canonical transforming growth factor-beta 1 (TGF-β1)/Smads and non-canonical janus-activated kinase 1 (JAK1)/singal transducer and activator of transcription 3 (STAT3) signaling pathways. Additionally, 6c owned a high safety profile with the LD50 value of over 1000 mg·kg−1 in mice. These results identified palmatine derivatives as a novel class of anti-fibrogenic agents, and provided powerful information for further structure optimization.

scholarly journals Effect of nanopolysaccharide (BSEPS) from Bacillus subtilis sp. on thioacetamide-induced liver fibrosis in rats

2019 ◽  
Vol 43 (1) ◽  
Author(s):  
Manal G. Mahmoud ◽  
Mohsen S. Asker ◽  
Mohamed E. El Awady ◽  
Amal I. Hassan ◽  
Nadia A. R. Zaharan ◽  
...  
Keyword(s):  
Bacillus Subtilis ◽  
Liver Fibrosis ◽  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Periodate Oxidation ◽  
Hepatic Tissue ◽  
Albino Rats ◽  
Gamma Glutamyl Transferase ◽  
Glutamyl Transferase ◽  
Tgf Β1

Abstract Background Nanomedicine contributes to the efficiency of pharmacological treatments and progresses rapidly. The present study was designed to produce exopolysaccharide (BSEPS) from Bacillus subtilis sp. strain reported in our previous study was further characterized, and its BSEPS for synthesis of the nanoparticle Ag-BSEPS using microwave heating to determine the possible effects of a prepared solution containing Ag-BSEPS versus thioacetamide (TAA) evoked liver fibrosis in Wister albino rats. Nanoparticles with silver (Ag) core have been synthesized in an aqueous solution after exposure of BSEPS to periodate oxidation. Animals were split into four groups: I - control rats, water ad libitum for 6 weeks; II - rats were injected with TAA 200 mg/kg-1 3 times/week for 4 weeks IP; III - Ag-BSEPS 100 mg/kg-1 IP twice a week for 6 weeks; and IV - TAA, as group II followed by Ag-BSEPS as group III. The antifibrotic effects of Ag-BSEPS were appraised by determining different hepatotoxicity indices, oxidative stress, and inflammatory and liver fibrosis markers. Results Nanoparticles were obtained with a diameter size range of 50–100 nm characterized by SEM and TEM without using any harmful reagents. Results evinced considerably reduced activity of liver functions such as transaminases (AST, ALT), gamma-glutamyl transferase (GGT), and alkaline phosphatase (ALP) in the group which received TAA followed by Ag-BSEPS compared to the other group which received only TAA. In the current results, the administration of Ag-BSEPS showed an improvement in the proinflammatory cytokines. On the contrary, the antioxidant enzymes in liver homogenates revealed significant improvement (concentration of glutathione peroxidase (GSH-PX), superoxide dismutase (SOD), and catalase (CAT) increases) in animals with TAA-induced liver damage followed by Ag-BSEPS. Moreover, the activities of the fibrotic markers transforming growth factor-beta 1(TGF-β1) and type III pro-collagen (PCIII) were increased in liver tissues in the group which was given TAA alone as compared to the controls. The percentage of fibrosis of hepatic tissue had a positive correlation with the levels of PCIII and TGF-β1, followed by Ag-BSEPS compared to the TAA group without nanocomposite treatment. Microscopic examinations revealed inhibitory effects of Ag-BSEPS on inflammatory changes and deterrent of liver fibrosis. Conclusion It was suggested that the biochemical and histological amelioration observed in Ag-BSEPS (100 mg/kg-1 twice a week for 6 weeks) treated the fibrotic rats.

scholarly journals GPR37 promotes the malignancy of lung adenocarcinoma via TGF-β/Smad pathway

Open Medicine ◽  
2020 ◽  
Vol 16 (1) ◽  
pp. 024-032
Author(s):  
Jian Wang ◽  
Min Xu ◽  
Dan-Dan Li ◽  
Wujikenayi Abudukelimu ◽  
Xiu-Hong Zhou
Keyword(s):  
Lung Adenocarcinoma ◽  
Biological Function ◽  
Migration And Invasion ◽  
Loss Of Function ◽  
Malignant Phenotype ◽  
Smad Pathway ◽  
Smad3 Phosphorylation ◽  
Poor Outcomes ◽  
Tgf Β1

AbstractThis paper aimed to research the function and in-depth mechanism of GPR37 in lung adenocarcinoma (LUAD). Herein, based on TCGA and Oncomine databases, we revealed that GPR37 was expressed at high levels in LUAD, and upregulation of GPR37 was related to the poor outcomes. Furthermore, biological function experiments in vitro were utilized to assess whether GPR37 impacts malignant phenotype of LUAD cells. Gain- or loss-of-function assays indicated that the upregulation of GPR37 contributed to improving the proliferation, migration, and invasion of LUAD cells in vitro, while knockdown of GPR37 can inhibit the malignant biological behaviors. Then, we found that depletion of GPR37 resulted in a decrease in the expression of TGF-β1 as well as the extents of Smad2 and Smad3 phosphorylation, while overexpression of GPR37 presented opposite outcomes. Altogether, our findings indicated that GPR37 is a potential oncogene of LUAD, and its promoting effects on the malignant progression of LUAD may be realized via TGF-β/Smad pathway.

Effect of a Porous Suture Containing Transforming Growth Factor Beta 1 on Healing After Rotator Cuff Repair in a Rat Model

2021 ◽  
pp. 036354652110285
Author(s):  
Jong Pil Yoon ◽  
Hun-Min Kim ◽  
Jin-Hyun Choi ◽  
Hae Rim Kang ◽  
Dong Hyun Kim ◽  
...  
Keyword(s):  
Rotator Cuff ◽  
Rat Model ◽  
Transforming Growth Factor Beta ◽  
Rotator Cuff Repair ◽  
Animal Experiment ◽  
Transforming Growth Factor ◽  
Group 3 ◽  
Growth Factor Beta ◽  
Cuff Repair ◽  
Tgf Β1

Background: The healing failure rate after rotator cuff repair is considerably high. Purpose: To evaluate the effect of a porous suture containing transforming growth factor beta 1 (TGF-β1) on the sustained release of TGF-β1 and rotator cuff healing in a rat model. Study Design: Controlled laboratory study. Methods: A porous suture was developed, and its tensile strength was measured. TGF-β1 was delivered using the porous suture, and a TGF-β1 release test and human fibroblast proliferation assay were performed. For the animal experiment, 30 rats were randomly allocated into 3 groups (n = 10 each). A bilateral supraspinatus tendon tear was made in all the rats, and repair was performed. Group 1 received repair only; group 2, repair and a single injection of TGF-β1; and group 3, repair using the porous suture containing TGF-β1. Eight weeks after repair, biomechanical and histological analyses were performed. Results: The porous suture was successfully developed with mechanical properties compatible with the conventional suture, and the sustained release of TGF-β1 from the porous suture was confirmed. In addition, the cell proliferation assay confirmed the biological safety of the porous suture. In the animal experiment, group 3 biomechanically exhibited the largest cross-sectional area and the highest ultimate failure load and ultimate stress (all P < .05). Histological examination revealed that group 3 showed significantly better collagen fiber density and tendon-to-bone maturation than did groups 1 and 2 (all P < .05). Conclusion: The porous suture containing TGF-β1 could sustainedly and safely release TGF-β1, and its use during rotator cuff repair could improve rotator cuff healing, as assessed on the basis of the biomechanical and histological changes in the rat model in this study. Considering the effectiveness, safety, and convenience of the porous suture without extra effort in surgery, the findings of the present study will have a far-reaching effect on the treatment of rotator cuff tears. Clinical Relevance: The porous suture containing TGF-β1 might improve healing after rotator cuff repair.

Attenuation of diethyl nitrosamine-induced hepatocellular carcinoma by taxifolin and/or alogliptin: The interplay between toll-like receptor 4, transforming growth factor beta-1, and apoptosis

2021 ◽  
pp. 096032712110084
Author(s):  
AM Kabel ◽  
HH Arab ◽  
MA Abd Elmaaboud
Keyword(s):  
Hepatocellular Carcinoma ◽  
Transforming Growth Factor Beta ◽  
Caspase 3 ◽  
Transforming Growth Factor ◽  
Liver Function Tests ◽  
Toll Like Receptor ◽  
Caspase 9 ◽  
Toll Like Receptor 4 ◽  
Growth Factor Beta ◽  
Tgf Β1

Hepatocellular carcinoma (HCC) is the most common form of liver malignancies worldwide. Alogliptin is an anti-diabetic that may have effective anticancer properties against many types of malignancies. Taxifolin is a flavonoid that has potent antioxidant, and anti-inflammatory properties. The objective of this study was to explore the impact of alogliptin and/or taxifolin on diethyl nitrosamine-induced HCC in rats. One hundred male Wistar rats were divided into five equal groups as follows: Control; HCC; HCC + Alogliptin; HCC + Taxifolin; and HCC + Alogliptin + Taxifolin group. The survival rate, liver function tests, tissue antioxidant enzymes, malondialdehyde (MDA), nuclear factor (erythroid derived 2)-like 2 (Nrf2), transforming growth factor beta 1 (TGF-β1), interleukin 1 alpha (IL-1α), and toll-like receptor 4 (TLR4) were measured. Also, hepatic caspase 3, caspase 9, beclin-1, and c-Jun NH2-terminal kinase (JNK) in addition to serum alpha-fetoprotein (AFP) and α-L-Fucosidase (AFU) were assessed. Specimens of the liver were subjected to histopathological examination. Alogliptin and/or taxifolin induced significant improvement of liver function tests with significant increase in the survival rate, tissue antioxidant enzymes, Nrf2, caspase 3, caspase 9, Beclin-1 and JNK activities associated with significant decrease in serum AFP and AFU, tissue MDA, TGF-β1, IL-1α and TLR4 expression compared to HCC group. These results were significant with taxifolin/alogliptin combination when compared to the use of each of these agents alone. In conclusion, taxifolin/alogliptin combination might be used as adjuvant therapy for attenuation of HCC.

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