Medicine in Drug Discovery (Jun 2022)

Discovery of eukaryotic cellular receptor for Withaferin A, a multifaceted drug from Withania somnifera plant

  • Varsha D. Shiragannavar,
  • Nirmala G. Sannappa Gowda,
  • Prasanna K. Santhekadur

Journal volume & issue
Vol. 14
p. 100127

Abstract

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Withaferin A is a dietary natural compound from a very popular Ayurvedic plant called Ashwagandha (Withania Somnifera). Since the discovery of Withaferin A and its initial isolation and characterization in 1965, a plethora of elegant molecular and biochemical studies have shown the potent beneficial effects of this compound on various diseases including cancer and have strongly established Withaferin A as a potent multifaceted pharmaceutical drug. Recently, we have shown the anti-tumor effect of Withaferin A on the various hallmarks of Hepatocellular Carcinoma (HCC) via targeting nuclear receptor and transcription factor Liver X receptor-α (LXR-α). These studies have also shown the novel function of LXR-α and have established LXR-α as a specific cellular receptor for Withaferin A. In this mini-review, we discussed comprehensively some of the important supporting experimental evidences that led to the discovery of this new cellular nuclear receptor for Withaferin A. Here, we also discussed how Withaferin A acts on LXR-α and negatively regulates NF-κB transcription factor and ameliorates HCC proliferation, migration and invasion.

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