Treatment of adult and pediatric high-grade gliomas with Withaferin A: antitumor mechanisms and future perspectives
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.
KeywordsBrain cancer High-grade glioma Withaferin A Experimental therapy Chemotherapy Mechanisms of action Astrocytoma Glioblastoma
We would like to thank the Mystic Force Foundation for their continued support of our research.
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Conflict of interest
The authors declare that they have no financial or other conflicts of interest in relation to this research and its publication.
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