Treatment of adult and pediatric high-grade gliomas with Withaferin A: antitumor mechanisms and future perspectives.

J Nat Med

Department of Neurological Surgery, Lois Pope Life Center, Miller School of Medicine, University of Miami Brain Tumor Initiative, 5th Floor, 1095 NW 14th Terrace, Miami, FL 33136, USA.

Published: January 2017

Resistance mechanisms employed by high-grade gliomas allow them to successfully evade current standard treatment of chemotherapy and radiation treatment. Withaferin A (WA), utilized in Ayurvedic medicine for centuries, is attracting attention for its antitumor capabilities. Here we review pertinent literature on WA as a high-grade glioma treatment, and discuss the cancerous mechanisms it affects. WA is relatively nontoxic and has shown potential in crossing the blood-brain barrier. WA prevents p53 alterations and inactivates overexpressed MDM2 through ARF and ROS production. Furthermore, WA upregulates Bax, inducing mitochondrial death cascades, inhibits mutated Akt, mTOR, and NF-κB pathways, and inhibits angiogenesis in tumors. Therapy with WA for high-grade gliomas is supported through the literature. Further investigation is warranted and encouraged to fully unearth its abilities against malignant gliomas.

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Source
http://dx.doi.org/10.1007/s11418-016-1020-2DOI Listing

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