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http://dx.doi.org/10.5352/JLS.2013.23.3.462

Anti-cancer Effects and Molecular Mechanisms of Withaferin A  

Woo, Seon Min (Department of Immunology, School of Medicine, Keimyung University)
Min, Kyoung-Jin (Department of Immunology, School of Medicine, Keimyung University)
Kwon, Taeg Kyu (Department of Immunology, School of Medicine, Keimyung University)
Publication Information
Journal of Life Science / v.23, no.3, 2013 , pp. 462-469 More about this Journal
Abstract
Withaferin A is a steroidal lactone purified from the Indian medicinal plant Withania somnifera. It exhibits a wide variety of activities, including anti-tumor, anti-inflammation, and immunomodulation properties. In this review, we focused on the anti-cancer effects of withaferin A. Withaferin A inhibits cell proliferation, metastasis, invasion, and angiogenesis in cancer cells. Furthermore, it sensitized irradiation, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-, and doxorubicin-mediated apoptosis. The results showed that multiple mechanisms were involved in withaferin A-mediated anti-cancer effects. First, withaferin A increased intracellular reactive oxygen species (ROS) production and induced ER stress- and mitochondria-mediated apoptosis. Second, withaferin A inhibited the signaling pathways (Jak/STAT, Akt, Notch, and c-Met), which are important in cell survival, proliferation, and metastasis. Third, it induced apoptosis and inhibited cancer cell migration through the up-regulation of prostate apoptosis protein-4 (Par-4). Finally, withaferin A up-regulated pro-apoptotic protein expression levels through the inhibition of proteasome activity. Our findings suggested that withaferin A is a potential, potent therapeutic agent.
Keywords
Anti-cancer effect; apoptosis; sensitization; signaling pathway; withaferin A;
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