Integrating Tradition and Innovation: The Role of Withania somnifera in Cancer Therapeutics

Abstract

Medicinal plants have been integral to healing in local communities for thousands of years and are crucial for approximately 85% of the global population. They are also a major source of drug discovery, with 80% of synthetic drugs deriving from them. Withania somnifera (WS), a prominent Rasayana botanical in Ayurveda, is renowned for its immunomodulatory, anti-aging, adaptogenic, and rejuvenating effects. WS exhibits therapeutic potential in cancer management due to its diverse biological activities. Major Phytoconstituent of WS like Withaferin-A (Wi-A) and Withanone has shown notable anticancer properties. Phytoconstituents of WS also have the potential to induce cell cycle arrest by downregulating cyclin B1, cyclin A, Cdk2, and p-Cdc2, while increasing p-Chk1 and p-Chk2 levels. It also affects HPV E6 and E7 oncoproteins, accumulates p53, and enhances p21WAF1 levels. Additionally, decreases STAT3 levels, promotes p53-mediated apoptosis (increasing Bcl2, Bax, caspase-3, cleaved PARP, and Par-4), and disrupts AKT and EMT signaling. These findings underline WS potential as a natural anticancer agent, with reported effects across various cancer types, including oxidative stress-induced mitochondrial dysfunction leading to programmed cell death.