Gliomas are the most frequent type of
primary brain tumor in adults. Their highly proliferative nature, complex cellular composition, and ability to escape
therapies have confronted investigators for years, hindering the advancement toward an effective treatment. Agents that are safe and can be administered as dietary supplements have always remained priority to be most feasible for
cancer therapy. Withania somnifera (
ashwagandha) is an essential ingredient of Ayurvedic preparations and is known to eliminate
cancer cells derived from a variety of peripheral tissues. Although our previous studies have addressed the in vitro anti-proliferative and differentiation-inducing properties of
ashwagandha on neuronal cell lines, in vivo studies validating the same are lacking. While exploring the mechanism of its action in vitro, we observed that the
ashwagandha water extract (ASH-WEX) induced the G2/M phase blockade and caused the activation of multiple pro-apoptotic pathways, leading to suppression of
cyclin D1, bcl-xl, and p-Akt, and reduced the expression of polysialylated form of
neural cell adhesion molecule (
PSA-NCAM) as well as the activity of
matrix metalloproteinases. ASH-WEX reduced the intracranial
tumor volumes in vivo and suppressed the
tumor-promoting
proteins p-
nuclear factor kappa B (NF-κB), p-Akt,
vascular endothelial growth factor (
VEGF),
heat shock protein 70 (HSP70),
PSA-NCAM, and
cyclin D1 in the rat model of orthotopic
glioma allograft. Reduction in
glial fibrillary acidic protein (GFAP) and upregulation of
mortalin and
neural cell adhesion molecule (
NCAM) expression specifically in
tumor-bearing tissue further indicated the anti-
glioma efficacy of ASH-WEX in vivo. Combining this enhanced understanding of the molecular mechanisms of ASH-WEX in
glioma with in vivo model system offers new opportunities to develop therapeutic strategy for safe, specific, and effective formulations for treating
brain tumors.