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Molecular Targets and Mechanisms of Cancer Prevention and Treatment by Withaferin A, A Naturally Occurring Steroidal Lactone

The AAPS Journal volume 16, pages 1–10 (2014)Cite this article

Abstract

The plants used in Ayurvedic medicine, which has been practiced in India for thousands of years for the treatment of a variety of disorders, are rich in chemicals potentially useful for prevention and treatment of cancer. Withania somnifera (commonly known as Ashwagandha in Ayurvedic medicine) is one such medicinal plant whose anticancer value was realized over four decades ago after isolation of a crystalline steroidal compound (withaferin A) from the leaves of this shrub. The root and leaf extracts of W. somnifera are shown to confer protection against chemically-induced cancers in experimental rodents, and retard tumor xenograft growth in athymic mice. Anticancer effect of W. somnifera is generally attributable to steroidal lactones collectively referred to as withanolides. Withaferin A (WA) appears most active against cancer among structurally divergent withanolides isolated from the root or leaf of W. somnifera. Cancer-protective role for WA has now been established using chemically-induced and oncogene-driven rodent cancer models. This review summarizes the key in vivo preclinical studies demonstrating anticancer effects of WA. Molecular targets and mechanisms likely contributing to the anticancer effects of WA are also discussed. Finally, challenges in clinical development of WA for the prevention and treatment of cancer are highlighted.

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ACKNOWLEDGMENTS

The work cited in this article from the authors’ laboratory was supported by the United States Public Health Service Grant CA142604-04 (to SVS).

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  1. Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Avani R. Vyas & Shivendra V. Singh

  2. University of Pittsburgh Cancer Institute, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

    Avani R. Vyas & Shivendra V. Singh

  3. 2.32A Hillman Cancer Center Research Pavilion, University of Pittsburgh Cancer Institute, 5117 Centre Avenue, Pittsburgh, Pennsylvania, 15213, USA

    Shivendra V. Singh

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  1. Avani R. Vyas
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Correspondence to Shivendra V. Singh.

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Vyas, A.R., Singh, S.V. Molecular Targets and Mechanisms of Cancer Prevention and Treatment by Withaferin A, A Naturally Occurring Steroidal Lactone. AAPS J 16, 1–10 (2014). https://doi.org/10.1208/s12248-013-9531-1

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KEY WORDS

  • apoptosis
  • autophagy
  • cell cycle
  • chemoprevention
  • signal transduction
  • withaferin A