Up-regulation of vimentin expression is one of the hallmarks of the epithelial-mesenchymal transition that accompanies the transformation of pre-metastatic to metastatic cancer cells. Withaferin A is a steroidal lactone present in W. somnifera that at 2-25 μM has been shown to bind to and induce aggregation of vimentin intermediate filaments in cultured endothelial cells and fibroblasts, causing apoptosis. As such, it has been proposed as an anti-tumor agent to target metastatic cells that up-regulate vimentin expression. At 2 mg/kg, withaferin A exhibits potent inhibition of angiogenesis in a mouse model of injury-induced corneal neovascularization. Withaferin A can also induce perinuclear aggregates in other intermediate filament networks including peripherin, neurofilament-triplet protein, and keratin as well as disrupt the organization of microtubules and actin/microfilaments.
