Evaluating anticancer properties of Withaferin A—a potent phytochemical

Abstract

Withaferin A is a C28 steroidal lactone derived from the plant Withania somnifera, commonly known as Ashwagandha. Withaferin A has received great attention for its anticancer properties noted in cancer cells of various origins. Extracts of Withania somnifera have been used in traditional Ayurvedic and Unani Indian medicine for their various pharmacological benefits. In recent years, Withania somnifera or Ashwagandha extract has become popularized as a health supplement marketed for its stress and anxiety reducing effects. Withaferin A is one of the most studied withanolides extracted from Withania somnifera that has gained great attention for its anticancer, anti-inflammatory, metabolic, and pro-apoptotic effects. Extensive in vivo and in vitro studies have depicted Withaferin A’s interactions with key role players in cancerous activity of the cell to exert its pro-apoptotic effects. Withaferin A interactions with NF-κB, STAT, Hsp90, ER-α, p53, and TGF-β have noted inhibition in cancer cell proliferation and cell cycle arrest in G2/M stage, ultimately leading to apoptosis or cell death. This review highlights pro-apoptotic properties of Withaferin A including generation of reactive oxidative species, Par-4 activation, endoplasmic reticulum stress (ER) induction, and p53 activation. Analysis of Withaferin A’s involvement in various oncogenic pathways leading to malignant neoplasm and its pharmacologic activity in conjunction with various cancer drugs provides promising evidence in therapeutic potential of Withaferin A as a cancer treatment.

Exploring the efficacy and safety of a novel standardized ashwagandha (Withania somnifera) root extract (Witholytin®) in adults experiencing high stress and fatigue in a randomized, double-blind, placebo-controlled trial

“…Future studies should include other measures of oxidative stress, such as myeloperoxidase and total antioxidant capacity, and more direct measures of inflammation such as C-reactive protein, tumor necrosis factor-alpha, and/or interleukin-6. These tests may be useful since ashwagandha has demonstrated anti-inflammatory and antioxidant properties (Atteeq, 2022; Kumar et al, 2022; Saggam et al, 2021). Also, indirect measures of HPA axis activation were used in the present study.…”

Phyto‐therapeutic potential of Withania somnifera: Molecular mechanism and health implications

“…Further, WN docked mortalin onto the p53 binding site, removed mortalin p53 complex and reactivated p53 which results in cell growth arrest in the case of MCF-7, U2OS, and HT1080 at conc. 5-15 μg/mL ( are expressed more heavily after taking Withaferin A (Atteeq, 2022).…”

“…Recent studies have started pinpointing scientific validation of bioactivities with molecular experimental evidences (Ha et al, 2022). The regulation of numerous receptors by W. somnifera bioactive substances was demonstrated using molecular docking, network pharmacology, and dynamic simulation-based techniques to efficiently manage diverse neurological illnesses , 2022Shukla et al, 2022). In the same context, a further investigation was carried out using a combination of in vitro and in silico network pharmacology-based methods (Mitra et al, 2022).…”

A Cancer Prevention and Treatment Opportunity

“…For example, withaferin A -a promising anti-cancer constituent of the Ayurvedic medicinal plant Withania somnifera-reduces MDSCs function [66]. Nevertheless, pregnant women should avoid Withania somnifera tonic as it may induce abortion at high doses [67]. In ancient Rome and Greece, women used silphium, an oral herbal contraceptive.…”