Abstract
Chemotherapy is one of the prime treatment options for cancer. However, the key issues with traditional chemotherapy are recurrence of cancer, development of resistance to chemotherapeutic agents, affordability, late-stage detection, serious health consequences, and inaccessibility. Hence, there is an urgent need to find innovative and cost-effective therapies that can target multiple gene products with minimal adverse reactions. Natural phytochemicals originating from plants constitute a significant proportion of the possible therapeutic agents. In this article, we reviewed the advances and the potential of Withania somnifera (WS) as an anticancer and immunomodulatory molecule. Several preclinical studies have shown the potential of WS to prevent or slow the progression of cancer originating from various organs such as the liver, cervix, breast, brain, colon, skin, lung, and prostate. WS extracts act via various pathways and provide optimum effectiveness against drug resistance in cancer. However, stability, bioavailability, and target specificity are major obstacles in combination therapy and have limited their application. The novel nanotechnology approaches enable solubility, stability, absorption, protection from premature degradation in the body, and increased circulation time and invariably results in a high differential uptake efficiency in the phytochemical’s target cells. The present review primarily emphasizes the insights of WS source, chemistry, and the molecular pathways involved in tumor regression, as well as developments achieved in the delivery of WS for cancer therapy using nanotechnology. This review substantiates WS as a potential immunomodulatory, anticancer, and chemopreventive agent and highlights its potential use in cancer treatment.
Highlights
Introduction published maps and institutional affilCancer is only second to heart disease as the leading cause of mortality globally.In 2022, the American Cancer Society reported about 1,918,030 new cases of cancer and609,360 cancer-related mortalities in the United States alone [1]
There were no significant differences in the stability of Withaferin A in male rats and humans when tested in formulated gastric fluid, in intestinal microflora solution, and in liver microsomes
Recent reports have shown the ability of Withania somnifera (WS) root extracts to suppress lipogenesis in 22Rv1 cells, most likely by decreasing the expression levels of p-Akt and c-Myc, and this possibly indicates the mechanism of fatty acid metabolism in malignant cells and a novel strategy of inducing antitumor activity in prostate cancer [101].Kunimasa et al [128] found that Withaferin A
Summary
The 23 known Withania species are widely distributed in the arid regions of India, Baluchistan, Afghanistan, Sri Lanka, Congo, South Africa, Egypt, Morocco, and Jordan [33]. WS plant organs such as the root, leaf, fruit, and seed possess adequate bio-active chemicals that have been implicated in pronounced anticancer, anti-microbial, cardioprotective, and neuroprotective mechanisms [33–42]. The presence of withanolides, a group of steroidal lactones, is thought to be responsible for the pharmacological activity of WS roots [43]. The main physiologically active chemical molecules present are alkaloids (isopellertierine and anferine), steroidal lactones (withanolides, withaferins saponins with additional acyl group (sitoindoside VII and VIII), and withanoloides with. A chemo assessment of Ashwagandha revealed that its primary ingredients are alkaloids and steroidal lactones. Withanolides present in leaf possess a C28 steroidal nucleus, a C9 side chain, and a hexagonal lactone ring. The roots of ashwagandha include alkaloids (wide variation of 0.13–0.31%), starch, reducing carbohydrates, hentriacontane, glycosides, dulcitol, withaniol acid, and a neutral molecule.
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