Abstract
BackgroundThe survival rate of malignant tumors, and especially hepatocellular carcinoma (HCC), has not improved primarily because of uncontrolled metastasis. In our previous studies, we have reported that Terminalia catappa leaf extract (TCE) exerts antimetastasis effects on HCC cells. However, the molecular mechanisms of urokinase-type plasminogen activator (u-PA) in HCC metastasis have not been thoroughly investigated, and remain poorly understood.MethodsThe activities and protein levels of u-PA were determined by casein zymography and western blotting. Transcriptional levels of u-PA were detected by real-time PCR and promoter assays.ResultsWe found that treatment of Huh7 cells with TCE significantly reduced the activities, protein levels and mRNA levels of u-PA. A chromatin immunoprecipitation (ChIP) assay showed that TCE inhibited the transcription protein of nuclear factors SP-1 and NF-κB. TCE also did inhibit the effects of u-PA by reducing the phosphorylation of ERK1/2 pathway.ConclusionsThese results show that u-PA expression may be a potent therapeutic target in the TCE-mediated suppression of HCC metastasis.
Highlights
The survival rate of malignant tumors, and especially hepatocellular carcinoma (HCC), has not improved primarily because of uncontrolled metastasis
Effects of Terminalia catappa leaf extract (TCE) on the Protein Levels of urokinase-type plasminogen activator (u-PA) and its Endogenous Inhibitor plasminogen activator inhibitors (PAI)-1 Huh7 cells were treated with TCE (0, 25, 50, 75, and 100 μg/mL) in a serum-free conditional medium for 24 h and subjected to casein zymography for the analysis of u-PA activity
Effects of TCE in suppressing u-PA expression at a transcriptional level The results of mRNA testing, reverse transcription PCR (RT-PCR), real-time PCR, and promoter reporter assays revealed the inhibitory effects of TCE on u-PA mRNA expression in Huh7 cells
Summary
The survival rate of malignant tumors, and especially hepatocellular carcinoma (HCC), has not improved primarily because of uncontrolled metastasis. Cancer cells from the primary tumor invade neighboring tissue through the secretion of urokinase-type plasminogen activator (u-PA). This degrades the basement membrane and separates the intercellular matrix, penetrating the circulation system and causing cancer cell invasion and metastasis [5]. U-PA is involved in extracellular matrix (ECM) degradation and the invasion and metastasis of cancer cells by regulating the plasminogen/ plasmin system. U-PA initiates the activation of ECM-degrading enzymes, allowing tumor cells to invade the basement membrane and enter circulation [5,11,13]. Inhibiting the expression of u-PA can potentially be used to treat cancer metastasis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
