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...

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Bibliographic Details
Published in:Journal of natural medicines 2017, Vol.71 (1), p.16-26
Main Authors: Marlow, Megan M., Shah, Sumedh S., Véliz, Eduardo A., Ivan, Michael E., Graham, Regina M.
Format: Article
Language:English
Subjects:
Adult
Angiogenesis
Ayurvedic medicine
Biomedical and Life Sciences
Biomedicine
Blood-brain barrier
Brain cancer
Brain Neoplasms - drug therapy
Brain Neoplasms - pathology
Cancer therapies
Chemotherapy
Complementary & Alternative Medicine
Glioma
Glioma - drug therapy
Glioma - pathology
Holistic medicine
Humans
Medicinal Chemistry
Pediatrics
Pharmacology/Toxicology
Pharmacy
Phytochemicals
Plant Sciences
Review
Tumors
Withanolides - administration & dosage
Withanolides - therapeutic use
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Summary: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.
ISSN:1340-3443
1861-0293
DOI:10.1007/s11418-016-1020-2