Withaferin A is a steroid lactone initially produced by Withania somnifera that exhibits anticancer chemotherapeutic, chemopreventive, and anti-inflammatory activities. Withaferin A inhibits vimentin, an intermediate filament, preventing breast cancer cell growth in vitro and in vivo. Withaferin A also increases phosphorylation of JNK, ERK, and p38 MAPK and increases levels of Mcl-1, inducing apoptosis in other in vitro models of breast cancer. Across other breast cancer cell lines, withaferin A increases activation of p53, downregulates expression of ERα, and activates Notch2 and Notch4, inhibiting cellular migration and growth. In ovarian cancer cells, withaferin A downregulates expression of Notch1, Notch3, chc25C, Akt, and Bcl-2, inhibiting growth and colony formation. Withaferin A also inhibits tumor growth of pancreatic xenografts in vivo through ATP-independent inhibition of heat shock protein 90 (HSP90). Additionally, this compound inhibits phosphorylation of IκB kinase, activation of NF-κB, and decreases levels of NO and iNOS in vitro.