AI Article Synopsis
- - Urokinase-type plasminogen activator receptor (uPAR) is key in inflammation and tumor spread, while docosahexaenoic acid (DHA), an omega-3 fatty acid, shows potential to counteract these processes.
- - This study explores how DHA affects uPAR expression, finding that DHA inhibits uPAR in a concentration-dependent way, linked to an increase in heme oxygenase-1 (HO-1) levels.
- - Results indicate that HO-1 plays a significant role in DHA's ability to decrease both uPAR expression and cell invasion, suggesting a possible therapeutic pathway for reducing tumor-related issues in humans.
Article Abstract
Urokinase-type plasminogen activator receptor (uPAR) plays a crucial role in inflammation and tumor metastasis. Docosahexaenoic acid (DHA), a representative omega-3 polyunsaturated fatty acid, has been shown to exhibit anti-inflammatory and anti-tumor properties. However, the mechanism by which DHA negatively regulates uPAR expression is not yet understood. The aim of this study was to investigate the effect of DHA on 12--tetradecanoylphorbol-13-acetate (TPA)-induced uPAR expression and potential role of heme oxygenase-1 (HO-1) in DHA-induced inhibition of uPAR in human endothelial ECV304 cells. Results showed that TPA induced uPAR expression in a time dependent manner, while DHA inhibited uPAR expression in a concentration-dependent manner. Moreover, treatment with DHA induced HO-1 expression in a time- and concentration-dependent manner. In addition, DHA-induced inhibition of uPAR expression and cell invasion in TPA-stimulated cells was reversed by si-HO-1 RNA. Induction of HO-1 by ferric protoporphyrin IX (FePP) inhibited TPA-induced uPAR expression, and this effect was abolished by treatment with the HO-1 inhibitor tin protoporphyrin IX (SnPP). Additionally, carbon monoxide, an HO-1 product, attenuated TPA-induced uPAR expression and cell invasion. Collectively, these data suggest a novel role of DHA-induced HO-1 in reducing uPAR expression and cell invasion in human endothelial ECV304 cells.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768974 | PMC |
| http://dx.doi.org/10.3389/fphar.2020.577302 | DOI Listing |
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