| Description: |
Sulforaphane is a cruciferous vegetable-derived isothiocyanate with promising antitumor, chemopreventive and therapeutic activities, it inhibits TPA-induced NF-κB activation and COX-2 expression in MCF-10A cells by blocking two distinct signaling pathways mediated by ERK1/2-IKKα and NAK-IKKβ. Sulforaphane may exert a significant neuroprotective effect on cholinergic deficit and cognitive impairment, it also has anti-inflammatory effect, at least ,in part,associated with interfering with the NF-κB pathway. |
| In vitro: |
| J Biosci Bioeng. 2015 Jan;119(1):35-42. | | Sulforaphane down-regulates SKP2 to stabilize p27(KIP1) for inducing antiproliferation in human colon adenocarcinoma cells.[Pubmed: 25070589] | Sulforaphane is a cruciferous vegetable-derived isothiocyanate with promising chemopreventive and therapeutic activities. Induction of proliferation arrest and apoptosis principally contribute to Sulforaphane's anticancer activity, but the precise molecular mechanisms remain elusive. The oncoprotein SKP2 is a key component of the SKP1-CULLIN1-F-box (SCF) E3 ligase complex and is responsible for directing SCF-mediated degradation of cyclin-dependent kinase inhibitor p27(KIP1) to promote cell proliferation.
METHODS AND RESULTS:
We herein provide the first evidence supporting the critical involvement of the SKP2-p27(KIP1) axis in Sulforaphane-induced antiproliferation in various human colon adenocarcinoma cell lines. Specifically, Sulforaphane markedly suppressed the levels of bromodeoxyuridine (BrdU) incorporation and clonogenicity in all tested cell lines, illustrating the antiproliferative effect of Sulforaphane. Of note, Sulforaphane-induced antiproliferation was accompanied with down-regulation of SKP2, leading to the stabilization and thus up-regulation of p27(KIP1). Additionally, Sulforaphane was found to down-regulate SKP2 mainly through transcriptional repression, as Sulforaphane lowered SKP2 mRNA expression and the SKP2 promoter activity. Furthermore, Sulforaphane treatment led to the activation of both AKT and ERK, thus ruling out the possibility that Sulforaphane down-regulates SKP2 by inhibiting AKT or ERK. Notably, Sulforaphane-elicited suppression of BrdU incorporation and clonogenicity were significantly rescued in the context of SKP2 overexpression or p27(KIP1) depletion, therefore highlighting the important role of SKP2 down-regulation and the ensuing stabilization of p27(KIP1) in Sulforaphane-induced antiproliferation.
CONCLUSIONS:
Collectively, these data expand our molecular understanding about how Sulforaphane elicits proliferation arrest, but also implicate the application of Sulforaphane in therapeutic modalities targeting SKP2. | | J Nutr Biochem. 2014 Aug;25(8):824-33. | | Sulforaphane reduces vascular inflammation in mice and prevents TNF-α-induced monocyte adhesion to primary endothelial cells through interfering with the NF-κB pathway.[Pubmed: 24880493] | Sulforaphane, a naturally occurring isothiocyanate present in cruciferous vegetables, has received wide attention for its potential to improve vascular function in vitro. However, its effect in vivo and the molecular mechanism of Sulforaphane at physiological concentrations remain unclear.
METHODS AND RESULTS:
Here, we report that a Sulforaphane concentration as low as 0.5 μM significantly inhibited tumor necrosis factor-α (TNF-α)-induced adhesion of monocytes to human umbilical vein endothelial cells, a key event in the pathogenesis of atherosclerosis both in static and under flow conditions. Such physiological concentrations of Sulforaphane also significantly suppressed TNF-α-induced production of monocyte chemotactic protein-1 and adhesion molecules including soluble vascular adhesion molecule-1 and soluble E-selectin, key mediators in the regulation of enhanced endothelial cell-monocyte interaction. Furthermore, Sulforaphane inhibited TNF-α-induced nuclear factor (NF)-κB transcriptional activity, Inhibitor of NF-κB alpha (IκBα) degradation and subsequent NF-κB p65 nuclear translocation in endothelial cells, suggesting that Sulforaphane can inhibit inflammation by suppressing NF-κB signaling. In an animal study, Sulforaphane (300 ppm) in a mouse diet significantly abolished TNF-α-increased ex vivo monocyte adhesion and circulating adhesion molecules and chemokines in C57BL/6 mice. Histology showed that Sulforaphane treatment significantly prevented the eruption of endothelial lining in the intima layer of the aorta and preserved elastin fibers' delicate organization, as shown by Verhoeff-van Gieson staining. Immunohistochemistry studies showed that Sulforaphane treatment also reduced vascular adhesion molecule-1 and monocyte-derived F4/80-positive macrophages in the aorta of TNF-α-treated mice.
CONCLUSIONS:
In conclusion, Sulforaphane at physiological concentrations protects against TNF-α-induced vascular endothelial inflammation, in both in vitro and in vivo models. This anti-inflammatory effect of Sulforaphane may be, at least in part, associated with interfering with the NF-κB pathway. |
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| In vivo: |
| Pharmacol Res. 2014 Jul;85:23-32. | | Sulforaphane alleviates scopolamine-induced memory impairment in mice.[Pubmed: 24836869] | Sulforaphane, an organosulfur compound present in cruciferous vegetables, has been shown to exert neuroprotective effects in experimental in vitro and in vivo models of neurodegeneration.
METHODS AND RESULTS:
To determine whether Sulforaphane can preserve cognitive function, we examined its effects on scopolamine-induced memory impairment in mice using the Morris water maze test. Sulforaphane (10 or 50mg/kg) was administered to C57BL/6 mice by oral gavage for 14 days (days 1-14), and memory impairment was induced by intraperitoneal injection of scopolamine (1mg/kg) for 7 days (days 8-14). Mice that received scopolamine alone showed impaired learning and memory retention and considerably decreased cholinergic system reactivity in the hippocampus and frontal cortex, as indicated by a decreased acetylcholine (ACh) level and an increased acetylcholinesterase (AChE) activity. Sulforaphane significantly attenuated the scopolamine-induced memory impairment and improved cholinergic system reactivity, as indicated by an increased ACh level, decreased AChE activity, and increased choline acetyltransferase (ChAT) expression in the hippocampus and frontal cortex. These effects of Sulforaphane on cholinergic system reactivity were confirmed in vitro. Sulforaphane (10 or 20μM) increased the ACh level, decreased the AChE activity, and increased ChAT expression in scopolamine-treated primary cortical neurons.
CONCLUSIONS:
These observations suggest that Sulforaphane might exert a significant neuroprotective effect on cholinergic deficit and cognitive impairment. |
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