title: Molecular targets and mechanisms of cancer prevention and treatment by withaferin a, a naturally occurring steroidal lactone.
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.
authors.affiliation: Department of Pharmacology & Chemical Biology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
authors.forename: Avani R
authors.initials: AR
authors.lastname: Vyas
authors.forename: Shivendra V
authors.initials: SV
authors.lastname: Singh
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001343:Autophagy / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D006801:Humans; D008515:Medicine, Ayurvedic; D009369:Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D008517:Phytotherapy; D010936:Plant Extracts / Q000493:pharmacokinetics / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects; D016896:Treatment Outcome; D032341:Withania; D054358:Withanolides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D010936:Plant Extracts; D054358:Withanolides; C009684:withaferin A
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