Abstract
Cancer, being the second leading cause of mortality, exists as a formidable health challenge. In spite of our enormous efforts, the emerging complexities in the molecular nature of disease progression limit the real success in finding an effective cancer cure. It is now conceivable that cancer is, in fact, a progressive illness, and the morbidity and mortality from cancer can be reduced by interfering with various oncogenic signaling pathways. A wide variety of structurally diverse classes of bioactive phytochemicals have been shown to exert anticancer effects in a large number of preclinical studies. Multiple lines of evidence suggest that withaferin-A can prevent the development of cancers of various histotypes. Accumulating data from different rodent models and cell culture experiments have revealed that withaferin-A suppresses experimentally induced carcinogenesis, largely by virtue of its potent anti-oxidative, anti-inflammatory, anti-proliferative and apoptosis-inducing properties. Moreover, withaferin-A sensitizes resistant cancer cells to existing chemotherapeutic agents. The purpose of this review is to highlight the mechanistic aspects underlying anticancer effects of withaferin-A.
Highlights
Despite the development of a wide variety of anticancer drugs, the global incidence of various cancers, and the mortality thereof, is still on the rise
AshwaMAX (40 mg/kg/day), a formulation of concentrated withaferin-A, was given by gavage to female nude mice receiving orthotopically administered human parietal-cortical glioblastoma (GBM2) cells transduced with lentiviral vectors expressing Green Fluorescent Protein (GFP) or firefly luciferase fusion proteins, and the growth of intracranial glioblastoma xenografts tumor was monitored by bioluminescence imaging (BLI)
This study revealed that the inhibitory effect of withaferin-A on breast cancer stem cells proliferation was partly mediated through cleavage of Notch-4 [99]
Summary
Despite the development of a wide variety of anticancer drugs, the global incidence of various cancers, and the mortality thereof, is still on the rise. A ggreeat ddeeal ooff rreesseeaarrcchh hhaass bbeeeenn ccoonndduucctteedd ttoo eelluucciiddaattee tthhee mmoolleeccuullaarr mmeecchhaanniisms uunndderlying anticancer effects of withaferin-A. This mini-review addresses the biochemical basis of antitumor potential of withaaffeerriinn--AA. The in vivo growth of soft tissue sarcoma cells implanted in female SCID (severely combined immunodeficient) mice was inhibited by i.p. administration of withaferin-A, which reduced cell proliferation and induced apoptosis via degradation of vimentin [16]. Contrary to these reports, oral administration of withaferin-A failed to inhibit the growth of HT1080 fibrosarcoma cells xenograft tumors in mice [17]
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