Withaferin A: A Pleiotropic Anticancer Agent from the Indian Medicinal Plant Withania somnifera (L.) Dunal

Abstract

Cancer represents the second most deadly disease and one of the most important public health concerns worldwide. Surgery, chemotherapy, radiation therapy, and immune therapy are the major types of treatment strategies that have been implemented in cancer treatment. Unfortunately, these treatment options suffer from major limitations, such as drug-resistance and adverse effects, which may eventually result in disease recurrence. Many phytochemicals have been investigated for their antitumor efficacy in preclinical models and clinical studies to discover newer therapeutic agents with fewer adverse effects. Withaferin A, a natural bioactive molecule isolated from the Indian medicinal plant Withania somnifera (L.) Dunal, has been reported to impart anticancer activities against various cancer cell lines and preclinical cancer models by modulating the expression and activity of different oncogenic proteins. In this article, we have comprehensively discussed the biosynthesis of withaferin A as well as its antineoplastic activities and mode-of-action in in vitro and in vivo settings. We have also reviewed the effect of withaferin A on the expression of miRNAs, its combinational effect with other cytotoxic agents, withaferin A-based formulations, safety and toxicity profiles, and its clinical potential.

Integrative vision in cancer research, prevention and therapy

“…We have recently discovered that serotonin, through its 5-HT 2a receptor and SIRT1–PGC-1α axis induces mitochondriogenesis in murine cortical primary neurons [ 37 ]. Mitochondrial number and quality of their functions are also modulated by polyphenols, influencing biogenesis, dynamics, and degradation [ 38 ]. There is an immense scope to study Ayurvedic modalities, including langhan and panchakarma, for their effects on mitochondria in cancer.…”

Phytochemicals as Invaluable Sources of Potent Antimicrobial Agents to Combat Antibiotic Resistance

“…Withaferin A (4-β,27-dihydroxy-1-oxo-5β,6β-epoxywitha-2,24-dienolide) is a natural steroidal lactone present in Withania somnifera and other members of the Solanaceae family, such as Acnistus arborescens [56]. Withaferin A displayed effective antibacterial activity against P. aeruginosa with a MIC and MBC of 60 µM and 80 µM, respectively.…”

Withaferin A and Celastrol Overwhelm Proteostasis

“…These studies have identified a large number of proteins and pathways, listed in Table 1 ( [4,; adapted from ref. [1]), that are affected by WA in different cell types. Refs.…”

“…Withaferin A (WA) is abundantly present in the roots and leaves of Withania somnifera , a plant that grows in India, the Middle East, and parts of Africa [ 1 , 2 ]. The plant has been used for ages in Ayurvedic medicine for the treatment of a wide variety of medical conditions.…”

“…The possibility of using WA as a broadly active cancer therapeutic has attracted particular attention and over the years has resulted in a multitude of studies employing various in vitro and in vivo cancer models (reviewed in, e.g., in refs. [ 1 , 2 ]). These studies have identified a large number of proteins and pathways, listed in Table 1 ([ 4 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]; adapted from ref.…”