scholarly journals Effects of Allium sativum Stem Extract on Growth and Migration in Melanoma Cells through Inhibition of VEGF, MMP-2, and MMP-9 Genes Expression

Molecules ◽  
2021 ◽  
Vol 27 (1) ◽  
pp. 21
Author(s):  
Da-Hye Gam ◽  
Jae-Hyun Park ◽  
Jun-Hee Kim ◽  
Dong-Ho Beak ◽  
Jin-Woo Kim

The present study investigated the effects of Allium sativum stem extract (ASE) on B16-F0 cell growth and metastasis. Evaluation of the effects of ASE on B16-F0 cells’ viability and migration showed that 0.5 mg/mL ASE inhibited B16-F0 cells’ growth by 30.2% and migration by 38.5%, which indicates that the ASE has anticancer and antimetastatic effects on B16-F0 cells. To study the anticancer and antimetastatic mechanism, mRNA levels of vascular endothelial growth factor (VEGF), matrix metalloproteinases-2 (MMP-2), and matrix metalloproteinases-9 (MMP-9) expressions were evaluated with reverse transcription polymerase chain reaction, and 0.25 and 0.5 mg/mL ASE was found to exert significant inhibition on mRNA expressions of VEGF, MMP-2, and MMP-9 in B16-F0 cells. Thus, ASE reduce extracellular matrix degradation through inhibitions of expression of MMP-2 and MMP-9, and also showed an angiogenesis inhibitory effect through reduction of VEGF expression. High-performance liquid chromatography analysis showed that among various polyphenols, gallic acid (2.1 mg/g) was a major compound of ASE. Overall, our results demonstrated that ASE inhibited the growth and migration of B16-F0 cells through downregulation of the VEGF, MMP-2, and MMP-9 genes expression, which indicates ASE could be applied for the prevention and treatment of melanoma.

2019 ◽  
Vol 2019 ◽  
pp. 1-16 ◽  
Author(s):  
Qin Yuan ◽  
Fei Yao ◽  
Liang Zhou ◽  
Guoqiang Liang ◽  
Xiudao Song ◽  
...  

Background. Clinically, Yu ping feng san (YPFS) has been extensively used as a medication for treating immune deficiency, and YPFS is combined with chemotherapy drugs to treat cancer, including hepatocellular carcinoma (HCC), lung cancer, and pancreatic cancer. Previous research has shown that YPFS has a therapeutic effect on HCC by improving the immunosuppressive state of the liver cancer microenvironment. The present study aimed to investigate the effect of YPFS on angiogenesis of HCC. Methods. High-performance liquid chromatography (HPLC) was used to certify the composition of YPFS. An orthotopic transplanted model of murine HCC was entrenched. Immunohistochemistry was used to observe the changes of the microvessel density (MVD). The MTT assay was used to detect the cell viability. ELISA was performed to analyze the expression of related factors. Western blot was used to analyze the protein expression. Tube formation assay was used to analyze the anti-angiogenic efficiency. Results. YPFS significantly reduced the tumor volume and weight, thus exerted the growth inhibitory effect. The level of MVD and VEGF was obviously decreased in YPFS-treated HCC-bearing mice, and the YPFS treatment also reduced the VEGF level in Hepa1-6 cells. Further study revealed that the expression of TSLP/TSLPR and p-STAT3/STAT3 was decreased by YPFS. The level of MVD and VEGF and the expression of TSLP/TSLPR and p-STAT3/STAT3 in tumor tissue and Hepa1-6 cells were suppressed by incubation with the anti-TSLP antibody, whereas treatment with the anti-TSLP antibody in YPFS-treated cells did not cause further significant inhibition compared with the cells treated only with YPFS. More importantly, YPFS inhibited proliferation, expression of p-STAT3/STAT3, and tube formation of HUVECs induced by TSLP. Conclusions. These results indicated that YPFS attenuated the activation of the TSLP-STAT3 signaling pathway by inhibiting the immune-related factor-TSLP, thereby inhibiting the formation of hepatic microvessels and exerting an anti-HCC effect.


Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 246 ◽  
Author(s):  
Filippo Randelli ◽  
Alessandra Menon ◽  
Alessio Giai Via ◽  
Manuel Mazzoleni ◽  
Fabio Sciancalepore ◽  
...  

Background: Greater Trochanter Pain Syndrome (GTPS) is the main reason for recalcitrant lateral hip pain. Gluteus medius and minimus tendinopathy plays a key role in this setting. An injectable medical compound containing collagen type I (MD-Tissue, Guna) has been produced with the aim to counteract the physiological and pathological degeneration of tendons. In this study we aimed at characterizing the effect of this medical compound on cultured human gluteal tenocytes, focusing on the collagen turnover pathways, in order to understand how this medical compound could influence tendon biology and healing. Methods: Tenocytes were obtained from gluteal tendon fragments collected in eight patients without any gluteal tendon pathology undergoing total hip replacement through an anterior approach. Cell proliferation and migration were investigated by growth curves and wound healing assay, respectively. The expression of genes and proteins involved in collagen turnover were analysed by real-time PCR, Slot blot and SDS-zymography. Results: Our data show that tenocytes cultured on MD-Tissue, compared to controls, have increased proliferation rate and migration potential. MD-Tissue induced collagen type I (COL-I) secretion and mRNA levels of tissue inhibitor of matrix metalloproteinases (MMP)-1 (TIMP-1). Meanwhile, lysyl hydroxylase 2b and matrix metalloproteinases (MMP)-1 and -2, involved, respectively, in collagen maturation and degradation, were not affected. Conclusions: Considered as a whole, our results suggest that MD-Tissue could induce in tenocytes an anabolic phenotype by stimulating tenocyte proliferation and migration and COL-I synthesis, maturation, and secretion, thus favouring tendon repair. In particular, based on its effect on gluteal tenocytes, MD-Tissue could be effective in the discouraging treatment of GTPS. From now a rigorous clinical investigation is desirable to understand the real clinical potentials of this compound.


2020 ◽  
Vol 477 (12) ◽  
pp. 2263-2279
Author(s):  
Prashant Deshmukh ◽  
Shruti Mathur ◽  
Gejo Gangadharan ◽  
Gopinatha Krishnappa ◽  
Nandakumar Dalavaikodihalli Nanjaiah ◽  
...  

Glioblastoma (GBM) is the most common primary brain malignancy, rarely amenable to treatment with a high recurrence rate. GBM are prone to develop resistance to the current repertoire of drugs, including the first-line chemotherapeutic agents with frequent recurrence, limiting therapeutic success. Recent clinical data has evidenced the BRD2 and BRD4 of the BET family proteins as the new druggable targets against GBM. In this relevance, we have discovered a compound (pyrano 1,3 oxazine derivative; NSC 328111; NS5) as an inhibitor of hBRD2 by the rational structure-based approach. The crystal structure of the complex, refined to 1.5 Å resolution, revealed that the NS5 ligand significantly binds to the N-terminal bromodomain (BD1) of BRD2 at the acetylated (Kac) histone binding site. The quantitative binding studies, by SPR and MST assay, indicate that NS5 binds to BD1 of BRD2 with a KD value of ∼1.3 µM. The cell-based assay, in the U87MG glioma cells, confirmed that the discovered compound NS5 significantly attenuated proliferation and migration. Furthermore, evaluation at the translational level established significant inhibition of BRD2 upon treatment with NS5. Hence, we propose that the novel lead compound NS5 has an inhibitory effect on BRD2 in glioblastoma.


Author(s):  
Xianyou Zeng ◽  
Changyan Zhu ◽  
Xianxin Zhu

Abstract DUSP4 is considered as an oncogenic gene. However, the effect of DUSP4 on the carcinogenesis of Clear cell Renal cell carcinoma (CCRCC) is still unclear. In this study, DUSP4 mRNA levels were significantly increased in CCRCC tissues and cell lines. Furthermore, DUSP4 overexpression promotes the proliferation, migration and tumorigenicity of CCRCC cells while DUSP4 silencing showed the opposite effects. Importantly, both of autophagic activity (LC3 conversion rate and LC3 puncta formation) and total death level promoted by DUSP4 silencing were reversed by treatment with 3-MA in CCRCC cells. Moreover, the proliferation and migration of CCRCC cells inhibited by DUSP4 silencing were also recovered by suppression of autophagy with 3-MA. In conclusion, DUSP4 serves as an oncogenic gene in CCRCC carcinogenesis due to its inhibitory effect on autophagic death, indicating the potential value of DUSP4 in the diagnosis and treatment of CCRCC.


2005 ◽  
Vol 60 (1-2) ◽  
pp. 83-90 ◽  
Author(s):  
Bun-ichi Shimizu ◽  
Hisashi Miyagawa ◽  
Tamio Ueno ◽  
Kanzo Sakata ◽  
Ken Watanabe ◽  
...  

An isolate of non-pathogenic Fusarium, Fusarium oxysporum 101-2 (NPF), induces resistance in the cuttings of morning glory against Fusarium wilt caused by F. oxysporum f. sp. batatas O-17 (PF). The effect of NPF on phenylpropanoid metabolism in morning glory cuttings was studied. It was found that morning glory tissues responded to treatment with NPF bud-cell suspension (108 bud-cells/ml) with the activation of phenylalanine ammonialyase (PAL). PAL activity was induced faster and greater in the NPF-treated cuttings compared to cuttings of a distilled water control. High performance liquid chromatography analysis of the extract from tissues of morning glory cuttings after NPF treatment showed a quicker induction of scopoletin and scopolin synthesis than that seen in the control cuttings. PF also the induced synthesis of these compounds at 105 bud-cells/ml, but inhibited it at 108 budcells/ ml. Possibly PF produced constituent(s) that elicited the inhibitory effect on induction of the resistance reaction. These compounds could potentially be useful as markers to detect early beginning interactions between Fusarium and morning glory tissues cuttings.


2019 ◽  
Vol 13 (02) ◽  
pp. 229-234 ◽  
Author(s):  
Ichaya Yiemwattana ◽  
Ruchadaporn Kaomongkolgit ◽  
Sodsi Wirojchanasak ◽  
Niratcha Chaisomboon

Abstract Objectives The aim of this study is to evaluate the inhibitory effects of M. alba stem extract (MSE) on the expression of matrix metalloproteinases (MMP)-1, MMP-9, and tissue inhibitors of metalloproteinase (TIMP)-1 in Porphyromonas gingivalis lipopolysaccharide (LPS)-activated-acute monocytic leukemia cell line (THP-1). Materials and Methods THP-1 cells were treated with noncytotoxic concentrations of MSE combined with 1 µg/mL of P. gingivalis LPS. The mRNA levels of MMP-1, MMP-9, and TIMP-1 were evaluated via quantitative real-time polymerase chain reaction. The secreted proteins in the culture media were detected by enzyme-linked immunosorbent assay. The degradation of inhibitor of kappa B-alpha (IκBα) protein was tracked by Western blotting. Statistical Analysis Comparisons in experiments were analyzed with analysis of variance followed by Tukey honestly significant difference comparison test. ResultsTwenty and 40 µg/mL of MSE significantly downregulated MMP-1 and MMP-9 genes and protein expression but upregulated the gene expression of TIMP-1 (p < 0.05). P. gingivalis LPS induced degradation of IκBα, while addition of MSE (20 and 40 µg/mL) increased IκBα cytosolic levels. MSE was able to suppress the P. gingivalis LPS-induced MMPs expression and also increased the gene expression of TIMP-1 via the inhibition of the cytoplasmic IκBα degradation in THP-1 cells. Conclusions The present observations suggest that MSE exerted a positive effect on the regulatory mechanism between MMPs and TIMP, which is an important implication for the therapeutic potential of MSE in periodontitis.


2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Guang-Yao Chen ◽  
Jia-Qi Chen ◽  
Xiao-Yu Liu ◽  
Yuan Xu ◽  
Jing Luo ◽  
...  

Total flavonoids of Rhizoma Drynariae (TFRD) have been shown to have beneficial effects on osteoarthritis (OA) clinically, but the mechanisms have not been elucidated. In this study, we investigated the effect of TFRD on articular cartilage in an OA rat model established by the Hulth method and in SW1353 chondrocytes induced by the proinflammatory factor interleukin-1β (IL-1β). The results showed that TFRD could alleviate the pathological changes in knee cartilage in OA model rats. In vivo, the qPCR analysis indicated that the mRNA levels of matrix metalloproteinases, MMP-1, MMP-3, and MMP-13, were decreased, while tissue inhibitor of matrix metalloproteinases- (TIMP-) 4 was increased in cartilage, and these changes could be partially prevented by TFRD. In vitro experiments showed that IL-1β could significantly increase the expression of MMP-1, MMP-3, and MMP-13 and decrease the expression of TIMP-4 in SW1353 cells at the mRNA and protein levels. TFRD could increase the expression of MMP-3 and MMP-13 and decrease the expression of TIMP-4. Transfection of siRNA and addition of pathway inhibitors were used to clarify that inhibition of NF- κ B and PI3K/AKT pathway decreased MMP-1, MMP-3, and MMP-13 and increased TIMP-4 expression. We also found that in IL-1β-induced SW1353 cells, TFRD pretreatment had a modest inhibitory effect on p-AKT (Ser473) and reversed the increase of nuclear factor kappa-B (NF- κ B ) p65 in nuclear fraction and the decrease of inhibitor of NF- κ B I κ B - α in the cytosolic fraction. Further immunofluorescence confirmed that TFRD can inhibit IL-1β-induced NF- κ B p65 translocation to the nucleus to some extent. In conclusion, TFRD showed chondroprotective effects by restoring the MMP/TIMP balance in OA models by suppressing the activation of the NF- κ B and PI3K/AKT pathways.


Author(s):  
Hams H. H. Alfattli ◽  
Ghufran Zuhair Jiber ◽  
Ghaidaa Gatea Abbass

This study which designed to evaluate the inhibitory effect of Ethanolic extract of (Quercusrobur) and Zinc oxide nanoparticles on the growth of one genus of enterobacteriacae (Salmonella). In vitro. For this purpose graduate concentrates for plant extract (50, 100, 200, 400 )mg/ml which prepared and compared with Zinc oxide nanoparticles of different concentration (2, 1, 0.5, 0.25) μg/ml,and examined. The result showed that the studied medicinal plant has antibacterial activity against this bacteria which used. The result showed that the plant has good activity in decrease the growth of this bacteria. The results of the study also showed that the nano-ZnO has very effective antibacterial action against the studied bacteria which was Salmonella,nanoparticles concentrations lead to increasing in the inhibition zones of tested bacterial growth. We also study the effect of three antibiotics Lomefloxacin (LOM), Ciprofloxacin (SIP) and Rifampin (RA) and the result showed,in a comparison within the tested bacteria,Salmonella had a significant inhibition increase in Lomefloxacin ; the ciprofloxacin showed effect on tested bacteria. However,Rifampin does not show any effect on tested bacteria.


2019 ◽  
Vol 1 (1) ◽  
pp. 100-104
Author(s):  
A. B. Filina ◽  
O. A. Svitich ◽  
Yu. I. Ammur ◽  
A. K. Golenkov ◽  
E. F. Klinushkina ◽  
...  

Аim. A study of CXCL12 effect on the migration of mononuclear cells isolated from healthy patients, from patients with myelomonoblastic leukemia before and after chemotherapy and the study of CCR4, EGFR and CXCL12 genes expression after exposure to CXCL12. Materials and methods. The chemotaxis of mononuclear cells (MNCs) of healthy donors and patients with myelomonoblastic leukemia was studied in a Boyden chamber, followed by isolation of RNA, reverse transcription and PCR-RV. Results. A significant increase in myelomonoblasic cell chemotaxis towards CXCL12 after chemotherapy was demonstrated, as well as a decrease in the expression of this chemokine in tumor cells before chemotherapy after exposure to CXCL12. Сonclusion. Presumably, the tumor cells themselves produce CXCL12 in large amounts, which is necessary for the disturbance of intercellular interactions and further intravasation, whose production may decrease with external stimulation by the same chemokine. CXCL12 also helps to increase the expression level of EGFR and CCR4, which leads to increased tumor proliferation and migration of tumor cells.


2019 ◽  
Vol 70 (2) ◽  
pp. 718-720
Author(s):  
Lucia Corina Dima-Cozma ◽  
Sebastian Cozma ◽  
Delia Hinganu ◽  
Cristina Mihaela Ghiciuc ◽  
Florin Mitu

Matrix metalloproteinases (MMPs) are the primary mediators of extracellular remodeling and their properties are useful in diagnostic evaluation and treatment. They are zinc-dependent proteases. MMPs have been involved in the mechanisms of atherosclerosis in various arterial areas, ischemic heart disease and myocardial infarction, atrial fibrillation and aortic aneurysms. Recently, MMP9 has been implicated in dyslipidemia and cholesterol synthesis by the liver. Increased MMP expression and activity has been associated with neointimal arterial lesions and migration of smooth muscle cells after arterial balloon dilation, while MMP inhibition decreases smooth muscle cell migration in vivo and in vitro.


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