Introduction
WITHAFERIN A, also referred to as D004, NSC 101088, used as an important medicinal herb for over 3000 years, is a steroidal lactone derived from Acnistus arborescens, Withania somnifera and other members of Solanaceae family. This natural product has wide range of pharmacological application comprising of anti-obesity, anti-inflammatory, anti-neoplastic, antiangiogenic, etc. WITHAFERIN A inhibits endothelial cells (HUVEC) sprouting (in vitro: IC50 = 12 nM and in vivo), activation of IKKβ (IC50= 0.5-1 μM), chymotrypsin-like activity of the 20S proteasome and cell proliferation of uveal melanoma cells (IC50= 0.90, 1.66, and 2.42 μM for OMM2.3, 92.1, and MEL290 cells, respectively). In vivo: studies using WA reduced tumor growth in 100% of animals (p = 0.015) In vitro: studies shows that WA is a potent drug that inhibits cell proliferation, shifts cell cycle arrest, and induces apoptosis in multiple UM cell lines
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