Description
Withaferin A (5119-48-2) displays potent antiangiogenesis activity inhibiting endothelial cell sprouting in vitro?(IC50?= 12 nM) and?in vivo.1?Potently inhibits NF-κB activation by preventing TNFα-induced activation of IKKβ.2?Covalently binds to the intermediate filament protein, vimentin3?inducing its disassembly and serine 56 phosphorylation4. Inhibits reactive gliosis and blocks TNFα-mediated neuronal apoptosis in?in vivo?models.5
Chemical Properties
Solid
Uses
Withaferin A is a promising anticancer constituent of Ayurvedic medicinal plant Withania somnifera. Withaferin A showed potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986). Withaferin A has recently been found to be a leptin sensitizer that can reduce the weight in obese mice fed in a high-fat diet (see C249500).
Definition
ChEBI: A withanolide that is 5,6:22,26-diepoxyergosta-2,24-diene-1,26-dione substituted by hydroxy groups at positions 4 and 27 (the 4beta,5beta,6beta,22R stereoisomer). Isolated from Phys
lis longifolia, it exhibits cytotoxic activity.
Biological Activity
Steroid lactone that displays anti-inflammatory, antitumor and antiangiogenic activity. Inhibits endothelial cells (HUVEC) spouting in vitro (IC 50 = 12 nM) and in vivo . Prevents NF- κ B activation by inhibiting activation of IKK β . Also inhibits chymotrypsin-like activity of the 20S proteasome.
target
ROS | NF-kB | p53 | STAT | PARP | Bcl-2/Bax | Caspase | TGF-β/Smad | TNF-α | COX | PGE | PI3K | Akt | JNK | p38MAPK
References
1) Mohan?et al.?(2004),?Withaferin A is a potent inhibitor of angiogenesis; Angiogenesis, 7 115
2) Kaileh?et al.?(2007),?Withaferin A strongly elicits IkappaB kinase beta hyperphosphorylation concomitant with inhibition of its kinase activity; J. Biol. Chem.,?282?4253
3) Bargagna-Mohan?et al.?(2007),?The tumor inhibitor and antiangiogenic agent withaferin A targets the intermediate filament protein vimentin; Chem. Biol.,?14?623
4) Thaiparambil?et al.?(2011),?Withaferin A inhibits breast cancer invasion and metastasis at sub-cytotoxic doses by inducing vimentin disassembly and serine 56 phosphorylation; Int. J. Cancer,?129?2744
5) Livne-Bar?et al.?(2016),?Pharmacologic inhibition of reactive gliosis blocks TNF-α-mediated neuronal apoptosis;?Cell Death Dis.,?7?e2386
