Explaining urokinase type plasminogen activator inhibition by amino-5-hydroxybenzimidazole and two naphthamidine-based compounds through quantum biochemistry

2018 ◽  
Vol 20 (35) ◽  
pp. 22818-22830 ◽  
Author(s):  
Christian Solis-Calero ◽  
Geancarlo Zanatta ◽  
Claudia do Ó Pessoa ◽  
Hernandes F. Carvalho ◽  
Valder N. Freire
Keyword(s):  
Tumor Growth ◽  
Plasminogen Activator ◽  
Therapeutic Target ◽  
Urokinase Plasminogen Activator ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Cancer Types ◽  
Tumor Growth And Metastasis ◽  
Slow Tumor Growth

Urokinase plasminogen activator (uPA) is a biomarker and therapeutic target for several cancer types whose inhibition has been shown to slow tumor growth and metastasis.

scholarly journals Specific Interference of Urokinase-type Plasminogen Activator Receptor and Matrix Metalloproteinase-9 Gene Expression Induced by Double-stranded RNA Results in Decreased Invasion, Tumor Growth, and Angiogenesis in Gliomas

2005 ◽  
Vol 280 (23) ◽  
pp. 21882-21892 ◽  
Author(s):  
Sajani S. Lakka ◽  
Christopher S. Gondi ◽  
Dzung H. Dinh ◽  
William C. Olivero ◽  
Meena Gujrati ◽  
...  
Keyword(s):  
Matrix Metalloproteinase ◽  
Tumor Growth ◽  
Plasminogen Activator ◽  
Tumor Invasion ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator ◽  
Antisense Approach ◽  
Plasminogen Activator Receptor ◽  
Metalloproteinase 9

We have previously demonstrated the effectiveness of adenovirus-mediated expression of antisense urokinase-type plasminogen activator receptor (uPAR) and matrix metalloproteinase-9 (MMP-9) in inhibiting tumor invasion in vitro and ex vivo. However, the therapeutic effect of the adenovirus-mediated antisense approach was shown to be transient and required potentially toxic, high viral doses. In contrast, RNA interference (RNAi)-mediated gene targeting may be superior to the traditional antisense approach, because the target mRNA is completely degraded and the molar ratio of siRNA required to degrade the target mRNA is very low. Here, we have examined the siRNA-mediated target RNA degradation of uPAR and MMP-9 in human glioma cell lines. Using RNAi directed toward uPAR and MMP-9, we achieved specific inhibition of uPAR and MMP-9. This bicistronic construct (pUM) inhibited the formation of capillary-like structures in both in vitro and in vivo models of angiogenesis. We demonstrated that blocking the expression of these genes results in significant inhibition of glioma tumor invasion in Matrigel and spheroid invasion assay models. RNAi for uPAR and MMP-9 inhibited cell proliferation, and significantly reduced the levels of phosphorylated forms of MAPK, ERK, and AKT signaling pathway molecules when compared with parental and empty vector/scrambled vector-transfected SNB19 cells. Furthermore, using RNAi to simultaneously target two proteases resulted in total regression of pre-established intracerebral tumor growth. Our results provide evidence that the use of hairpin siRNA expression vectors for uPAR and MMP-9 may provide an effective tool for cancer therapy.

scholarly journals Prostate Cancer Cell-Derived Urokinase-Type Plasminogen Activator Contributes to Intraosseous Tumor Growth and Bone Turnover

Neoplasia ◽  
2008 ◽  
Vol 10 (5) ◽  
pp. 439-449 ◽  
Author(s):  
Zhong Dong ◽  
Allen D. Saliganan ◽  
Hong Meng ◽  
Sanaa M. Nabha ◽  
Aaron L. Sabbota ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Turnover ◽  
Tumor Growth ◽  
Plasminogen Activator ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Type Plasminogen Activator ◽  
Urokinase Type Plasminogen Activator
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