A Perspective on Withania somnifera Modulating Antitumor Immunity in Targeting Prostate Cancer

Abstract

Medicinal plants serve as a lead source of bioactive compounds and have been an integral part of day-to-day life in treating various disease conditions since ancient times. Withaferin A (WFA), a bioactive ingredient of Withania somnifera, has been used for health and medicinal purposes for its adaptogenic, anti-inflammatory, and anticancer properties long before the published literature came into existence. Nearly 25% of pharmaceutical drugs are derived from medicinal plants, classified as dietary supplements. The bioactive compounds in these supplements may serve as chemotherapeutic substances competent to inhibit or reverse the process of carcinogenesis. The role of WFA is appreciated to polarize tumor-suppressive Th1-type immune response inducing natural killer cell activity and may provide an opportunity to manipulate the tumor microenvironment at an early stage to inhibit tumor progression. This article signifies the cumulative information about the role of WFA in modulating antitumor immunity and its potential in targeting prostate cancer.

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

“…In addition, the treatment led to the modulation of cyclinB1, PCNA, and p34, and altered the expression of p53-mediated apoptotic markers, such as Bcl-2, caspase-3, and PARP cleavage [ 95 ]. An oral dose of 3–5 mg/kg withaferin A attenuated the activation of Akt and stimulated Forkhead Box-O3a (FOXO3a)-mediated prostate apoptotic response-4 (Par-4) activation, effectively inhibiting the tumor progression in prostate cancer cells [ 96 , 97 , 98 ]. Several studies have also shown that colorectal adenocarcinoma cells treated with withaferin A significantly delay the mitotic cell cycle process by promoting the degradation of mitotic arrest deficiency 2 (Mad2), Cdc20, and the spindle assembly checkpoint (SAC) [ 99 ].…”

Ashwagandha Ethanol Extract Attenuates Sarcopenia-Related Muscle Atrophy in Aged Mice

“…In the realm of holistic health, it is often likened to ginseng for its stress-reducing capabilities, cognitive enhancements (e.g., memory improvement), and support for a robust immune system [ 21 ]. One of its remarkable features is its ability to modulate the immune system, striking a balance between the humoral and cellular responses of the adaptive immune system [ 22 ]. The therapeutic effects of W. somnifera are primarily attributed to its active constituents, including alkaloids, steroidal lactones (e.g., withanolides, withaferin A), and steroidal saponins [ 23 , 24 ].…”