Journal of Natural Medicines

, Volume 71, Issue 1, pp 16–26 | Cite as

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

  • Megan M. Marlow
  • Sumedh S. Shah
  • Eduardo A. Véliz
  • Michael E. Ivan
  • Regina M. Graham
Review

Abstract

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.

Keywords

Brain cancer High-grade glioma Withaferin A Experimental therapy Chemotherapy Mechanisms of action Astrocytoma Glioblastoma 

Notes

Acknowledgments

We would like to thank the Mystic Force Foundation for their continued support of our research.

Compliance with ethical standards

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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Copyright information

© The Japanese Society of Pharmacognosy and Springer Japan 2016

Authors and Affiliations

  • Megan M. Marlow
    • 1
  • Sumedh S. Shah
    • 1
  • Eduardo A. Véliz
    • 2
  • Michael E. Ivan
    • 1
  • Regina M. Graham
    • 1
  1. 1.Department of Neurological Surgery, Lois Pope Life Center, Miller School of MedicineUniversity of Miami Brain Tumor InitiativeMiamiUSA
  2. 2.Department of ChemistryUniversity of MiamiCoral GablesUSA

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