Withania somnifera - a magic plant targeting multiple pathways in cancer related inflammation

Abstract

Background: Deregulated inflammatory responses are known to play a pivotal role in cancer initiation and progression. Tumor microenvironment is associated with the presence of a diverse array of inflammatory reactions, which further help tumor growth, metastasis and drug resistance. Withania somnifera is known to curb proliferation of cancer cells and lower inflammatory responses.

Purpose: In order to minimize the inflammation, cancer treatments often include immunomodulatory drugs. However, given the side effects of both of the cytotoxic cancer drugs and synthetic immunomodulatory agents, there is a need to develop novel anti-inflammatory agents for improved cancer therapy. A number of reports indicate that bioactive phytochemicals derived from W. somnifera exhibit anti-inflammatory capabilities in cancer. A deeper look into the underlying molecular mechanisms implicated in W. somnifera mediated anti inflammation is lacking, which is essential to fully understand the potential of this magical plant in cancer. Therefore, in the present review we are summarizing various reports, which describe mechanistic understanding of W. somnifera in cancer related inflammation.

Study design and methodology: In order to gather information on the molecular pathways affected by W. somnifera in cancer related inflammation, 'PubMed' and 'Science Direct' databases were searched using keywords Withania, cancer inflammation, and Withaferin A. Selected literature was analyzed to cover the role of inflammation in cancer, usage and side effects of anti-inflammatory drugs, W. somnifera as an immunomodulatory agent in cancer, molecular pathways modulated by W. somnifera in various preclinical models, and clinical trials using W. somnifera as an anti-inflammatory agent.

Results: Upon literature survey we found that both W. somnifera extracts and Withaferin-A, exhibit anti inflammatory activities in various preclinical cancer models. W. somnifera modulates a number of signaling pathways such as NF-kB, JAK-STAT and AP1 to reduce cancer related inflammation. Anti inflammatory properties of W. somnifera might be effective in the treatment of drug resistance in cancers. Based on its promising effects against cancer associated inflammation in preclinical studies, W. somnifera derived products are being tested in clinical trials.

Conclusion: Several preclinical studies demonstrated anti-inflammatory potential of W. somnifera in a variety of cancers. While a few clinical trials are investigating the role of W. somnifera in various diseases, focused studies on its role in cancer related inflammation are lacking. Additionally, its anti-inflammatory effects offer targeting of senescence associated secretory phenotype (SASP), which is speculated to play a critical role in chemoresistance. Apart from targeting cancer cell proliferation, anti-inflammatory effects of Withania provide double advantage in cancer management. Therefore, clinical trials to target cancer related inflammation using W. somnifera as a drug, should be performed to validate its advantages in cancer therapy.

Keywords: Cyclooxygenase-2 (COX-2); Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB); Tumor inflammation, Cytokines; Withaferin A; Withania somnifera.