title: Treatment of adult and pediatric high-grade gliomas with Withaferin A: antitumor mechanisms and future perspectives.
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.
authors.affiliation: 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.
authors.forename: Megan M
authors.initials: MM
authors.lastname: Marlow
authors.affiliation: 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.
authors.forename: Sumedh S
authors.initials: SS
authors.lastname: Shah
authors.affiliation: Department of Chemistry, University of Miami, Coral Gables, FL 33146, USA.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Véliz
authors.affiliation: 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.
authors.forename: Michael E
authors.initials: ME
authors.lastname: Ivan
authors.affiliation: 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. RGraham@med.miami.edu.
authors.forename: Regina M
authors.initials: RM
authors.lastname: Graham
mesh_terms: D000328:Adult; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D054358:Withanolides / Q000008:administration & dosage / Q000627:therapeutic use*
chemical_list: D054358:Withanolides; C009684:withaferin A
keywords: Astrocytoma; Brain cancer; Chemotherapy; Experimental therapy; Glioblastoma; High-grade glioma; Mechanisms of action; Withaferin A