||6,7-Dihydroxycoumarin(Esculetin) has various biological and pharmaceutical properties including anti-edema, anti-inflammatory, anti-tumour, hepatoprotective, anti-osteoarthritis and anti-rheumatoid arthritis effects. It inhibits lipoxygenases (LOs), p42/44 MAPK activation, PI3-kinase activation, as well as NF-kappaB and AP-1 activation, it exhibits competitive inhibition against the oxidation of 3-(3,4-dihydroxyphenyl)- alanine by mushroom, the IC50 value of is 43 microM. |
|Int J Oncol. 2015 Jan;46(1):265-71. |
|Esculetin (6,7-dihydroxycoumarin): a potential cancer chemopreventive agent through suppression of Sp1 in oral squamous cancer cells.[Pubmed: 25310400]|
|Esculetin (6,7-Dihydroxycoumarin), a coumarin compound, is known to inhibit proliferation and induce apoptosis in several types of human cancer cells and is regarded as a promising chemotherapeutic agent.
METHODS AND RESULTS:
The purpose of the present study was to investigate the anti-proliferative effects of esculetin on two oral squamous cell carcinoma (OSCC) cell lines, HN22 and HSC4, through regulation of specificity protein 1 (Sp1). We examined the apoptotic effects of esculetin were measured by MTS assay, DAPI staining, Annexin V, PI staining, RT-PCR, western blot analysis and immunocytochemistry in HN22 and HSC4 cells. Taken together, the results of the present study indicate that esculetin had anti-proliferative effect on the growth of OSCC cells (HN22 and HSC4) in a dose- and time-dependent manner. The treatment of HN22 and HSC4 cells with esculetin led to a significant reduction in growth and induced apoptosis, followed by the regulation of Sp1 and Sp1 regulatory protein.
This indicates that esculetin inhibited cell growth and induced apoptosis by suppressing Sp1 in HN22 and HSC4 cells, suggesting it to be a potent anticancer drug candidate for oral cancer.
|Food Funct. 2014 Sep;5(9):2371-7. |
|Esculetin inhibits the inflammatory response by inducing heme oxygenase-1 in cocultured macrophages and adipocytes.[Pubmed: 25088305]|
METHODS AND RESULTS:
In this study, we investigated the anti-inflammatory effects of esculetin (6,7-Dihydroxycoumarin,ECT) through up-regulation of heme oxygenase-1 (HO-1) in cocultured macrophages and adipocytes. RAW264.7 macrophages and differentiated 3T3-L1 adipocytes were cocultured in serum-free Dulbecco's modified Eagle's medium with or without ECT for 24 h. Nitric oxide (NO), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1) production was measured in the coculture supernatant. ECT decreased the secretion of NO, TNF-α, and MCP-1. The expression of adipogenic proteins, including peroxisome proliferator-activated receptors γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα) in cocultured adipocytes and inducible nitric oxide synthase (iNOS) in cocultured macrophages, was inhibited by ECT. Additionally, HO-1 expression was induced in cocultured macrophages and adipocytes. Silencing of HO-1 expression increased the production of NO, TNF-α, and MCP-1 in cocultured cells, in spite of the presence of ECT.
This study demonstrated that ECT exhibited anti-inflammatory properties by inhibiting the production of proinflammatory cytokines in the interaction between adipocytes and macrophages through HO-1 expression. ECT may have the potential to improve chronic inflammation in obesity.
|Eur. J. Pharmacol., 1999, 370(3):297-305 |
|Esculetin suppresses proteoglycan metabolism by inhibiting the production of matrix metalloproteinases in rabbit chondrocytes.[Pubmed: 10334506]|
|The possible mechanism of the chondroprotective effect of 6,7-Dihydroxycoumarin (esculetin) was investigated using primary cultures of rabbit articular chondrocytes.
METHODS AND RESULTS:
Esculetin (EST) significantly suppressed the proteoglycan depletion and the release of pulse-labeled [35S]proteoglycan from the matrix layer of rabbit chondrocytes treated with recombinant human interleukin-1alpha. The matrix metalloproteinase inhibitor, 1,10-phenanthroline, also blocked the proteoglycan depletion and [35S]proteoglycan release. From these results, it is likely that recombinant human interleukin-1alpha-induced proteoglycan depletion is mediated by matrix metalloproteinases. Although esculetin did not directly inhibit collagenolytic activity in the culture media, it significantly suppressed the production of pro-matrix metalloproteinase-1/interstitial procollagenase and pro-matrix metalloproteinase-3/prostromelysin 1, accompanied by a decrease in the steady-state levels of their mRNAs.
These results suggest that esculetin is a therapeutically effective candidate for inhibition of cartilage destruction in osteoarthritis and rheumatoid arthritis.