scholarly journals 6-(1-oxobutyl)-5,8-dimetoxy-1,4-naphthoquinone inhibits the growth of MCF-7 cells via inhibition of angiogenesis and hypoxia inducible factor alpha

2005 ◽  
Vol 7 (S1) ◽  
Author(s):  
S-H Kim
Keyword(s):  
Hypoxia Inducible Factor ◽  
Inhibition Of Angiogenesis ◽  
Factor Alpha ◽  
Mcf 7

scholarly journals Nanoencapsulation of Hirudo medicinalis proteins in liposomes as a nanocarrier for inhibiting angiogenesis through targeting VEGFA in the Breast cancer cell line (MCF-7)

Bioimpacts ◽  
2021 ◽  
Author(s):  
Amir Shakouri ◽  
Houman Kahroba ◽  
Hamed Hamishekar ◽  
Jalal Abdolalizadeh
Keyword(s):  
Breast Cancer ◽  
Cancer Cells ◽  
Hypoxia Inducible Factor ◽  
Cancer Cell Line ◽  
Dapi Staining ◽  
Transmission Electron ◽  
Inhibition Of Angiogenesis ◽  
Blotting Technique ◽  
Endothelial Growth Factor ◽  
Mcf 7

Introduction: Breast cancer is the most serious cause of women’s death throughout the world. Using nanocarrier vehicles to the exact site of cancer upgrades the therapeutic efficiency of the drugs. Capsulation of active proteins in the vesicular liposomes’ hydrophilic core is essential to develop a therapeutic protein carrier system. We aimed to encapsulate the medicinal leech saliva extract (LSE) and assess the inhibition of angiogenesis of breast cancer cells by targeting vascular endothelial growth factor A (VEGFA). Methods: In this research, enhanced formulation of liposomal protein was determined by zeta potential analysis, droplet size, drug release assay, and transmission electron microscopy (TEM). Furthermore, a cytotoxicity assay of liposomal LSE was performed to determine the cytotoxic activity of components. For assessing the expression of VEGFA, P53, and hypoxia-inducible factor subunit alpha (HIF1a) genes, Real-Time PCR was applied. Results: Nano liposome was chosen as an enhanced formulation due to its much smaller size (46.23 nm). Liposomal LSE had more practical actions on the MCF-7 cells. As noticed by DAPI staining, apoptosis was extensively greater in treated MCF-7 cells. Wound healing assay demonstrated that MCF-7 cells could not sustain growth at the presence of liposomal LSE and expression of the VEGFA gene was declined in treated cells. Downregulation of VEGFA was evaluated with western blotting technique. Conclusion: It can be concluded that our investigation of the tests confirmed the fact that nano liposomal LSE is a novel promising formulation for anticancer drugs and can significantly improve the penetration of protein drugs to cancer cells.

scholarly journals Downregulation of integrins by von Hippel-Lindau (VHL) tumor suppressor protein is independent of VHL-directed hypoxia-inducible factor alpha degradation

2008 ◽  
Vol 86 (3) ◽  
pp. 227-234 ◽  
Author(s):  
Qingzhou Ji ◽  
Robert D. Burk
Keyword(s):  
Tumor Suppressor ◽  
Clear Cell ◽  
Hypoxia Inducible Factor ◽  
Intercellular Junctions ◽  
Suppressor Gene ◽  
Wild Type ◽  
Von Hippel Lindau ◽  
Degradation Activity ◽  
Factor Alpha ◽  
Vhl Tumor Suppressor Protein

Inactivation of the von Hippel-Lindau (VHL) tumor suppressor gene occurs in the majority of clear-cell renal cell carcinomas (RCCs). It was previously shown that VHL decreased the abundance of integrins α2, α5, and β1, which is consistent with VHL-associated changes in cell–cell and cell – extracellular matrix adhesions. We investigated the mechanism by which VHL downregulates integrins. Although VHL can target hypoxia-inducible factor alpha (HIFα) subunits for degradation, VHL-dependent reduction of integrins was independent of O2 concentration and HIFα levels. VHL reduced the half-lives of integrins, and this activity was blocked by proteasomal inhibition. Although ectopically expressed FLAG-VHL retained HIFα degradation activity, it neither downregulated integrins nor promoted adherens and tight intercellular junctions, in contrast to expressed wild-type VHL. Moreover, integrins co-immunoprecipitated with wild-type VHL, but not FLAG-VHL. These data indicate that the downregulation of integrins by VHL is distinct from the regulation of HIFα subunits by VHL, and suggests that the loss of this activity contributes to VHL-associated RCC development through disruption of adherens and tight junctions.

scholarly journals VHL inhibitor binding increases intracellular level of VHL

2021 ◽  
Author(s):  
Julianty Frost ◽  
Sonia Rocha ◽  
Alessio Ciulli
Keyword(s):  
Enzyme Inhibitor ◽  
Hypoxia Inducible Factor ◽  
High Specificity ◽  
Protein Levels ◽  
Tumour Suppressor Protein ◽  
Functional Characterisation ◽  
Vhl Protein ◽  
Factor Alpha ◽  
Vhl Disease ◽  
Protein Stabilisation

The vonHippel Lindau (VHL) protein is a tumour suppressor protein frequently mutated in the VHL disease, which functions as substrate recognition subunit of a Cul2 E3 ubiquitin ligase (CRL2VHL). CRL2VHL plays an important role in oxygen sensing, by binding and targeting Hypoxia Inducible Factor-alpha subunits (HIF-alpha) for ubiquitination and degradation. VHL is also commonly hijacked by heterobifunctional degrader molecules known as proteolysis-targeting chimeras (PROTACs). In previous work we reported the structure-based design and functional characterisation of VHL inhibitors (VH032 and VH298) that induce the HIF response in cells. Here, we use unbiased quantitative mass spectrometry to identify the proteomic changes elicited by the VHL inhibitor and compare this to hypoxia or broad-spectrum prolyl-hydroxylase domain (PHD) enzyme inhibitor IOX2. Our results demonstrate the VHL inhibitor selectively activates the HIF response that vastly overlaps with hypoxia- and IOX2-induced proteomic changes. Interestingly, VHL inhibitors were found to selectively upregulate a single protein, which is VHL itself. Our analysis revealed that this occurs via protein stabilisation of VHL isoforms and not via changes in transcript levels. Increased VHL levels upon VH298 treatment resulted in turn to reduced levels of HIF-1 protein. Our results demonstrate the high specificity of VHL inhibitors and suggest that use of these inhibitors would not produce overtly side effects due to prolonged HIF stabilisation. They also exemplify the concept that small-molecule binding induced protein stabilisation can increase protein levels inside cells.

scholarly journals Long-Term Alteration of Reactive Oxygen Species Led to Multidrug Resistance in MCF-7 Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Juan Cen ◽  
Li Zhang ◽  
Fangfang Liu ◽  
Feng Zhang ◽  
Bian-Sheng Ji
Keyword(s):  
Reactive Oxygen Species ◽  
Multidrug Resistance ◽  
Hypoxia Inducible Factor ◽  
Reactive Oxygen ◽  
Underlying Mechanism ◽  
Related Factor ◽  
Oxygen Species ◽  
Glutathione S Transferase ◽  
Mcf 7

Reactive oxygen species (ROS) play an important role in multidrug resistance (MDR). This study aimed to investigate the effects of long-term ROS alteration on MDR in MCF-7 cells and to explore its underlying mechanism. Our study showed both long-term treatments of H2O2 and glutathione (GSH) led to MDR with suppressed iROS levels in MCF-7 cells. Moreover, the MDR cells induced by 0.1 μM H2O2 treatment for 20 weeks (MCF-7/ROS cells) had a higher viability and proliferative ability than the control MCF-7 cells. MCF-7/ROS cells also showed higher activity or content of intracellular antioxidants like glutathione peroxidase (GPx), GSH, superoxide dismutase (SOD), and catalase (CAT). Importantly, MCF-7/ROS cells were characterized by overexpression of MDR-related protein 1 (MRP1) and P-glycoprotein (P-gp), as well as their regulators NF-E2-related factor 2 (Nrf2), hypoxia-inducible factor 1 (HIF-1α), and the activation of PI3K/Akt pathway in upstream. Moreover, several typical MDR mediators, including glutathione S-transferase-π (GST-π) and c-Myc and Protein Kinase Cα (PKCα), were also found to be upregulated in MCF-7/ROS cells. Collectively, our results suggest that ROS may be critical in the generation of MDR, which may provide new insights into understanding of mechanisms of MDR.

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