Withaferin A

Withaferin A is a steroid lactone that displays anti-inflammatory, antitumor and antiangiogenic activity, potently inhibits NF-κB activation by preventing the TNF-induced activation of IKKβ via a thioalkylation-sensitive redox mechanism; potently inhibits the chymotrypsin-like activity of a purified rabbit 20S proteasome (IC50=4.5 uM) and 26S proteasome in human prostate cancer cultures (at 5-10 uM) and xenografts (4-8 mg/kg/day), inhibits cell proliferation in HUVECs (IC50 =12 nM) . (In Vitro) :Withaferin A has antiinflammatory activity, and potently inhibits NF-kB activation by preventing the TNF-induced activation of Ik-B kinase beta via a thioalkylation-sensitive redox mechanism. Withaferin A also has anticancer activity. Withaferin A targets the IF protein vimentin, causes aggregation of vimentin filaments in bovine aortic endothelial cells (BAECs) at 3 μM, and induces vimentin fragmentation in endothelial cells at 10 μM. Withaferin A (0.5, 1.5 μM) alone or incombination with cisplatin (CIS) dose-dependently reduces tumorigenic potential of ALDH1 positive cancer stem cells (CSCs) . (In Vivo) :Withaferin A (2 mg/kg, i.p.) shows potent angiogenesis inhibitory activity via vimentin in mice. Withaferin A (2 mg/kg) combined with cisplatin (CIS) regulates the expression of ALDH1 marker, and downregulates the expression of securin in tumors collected from mice.