Abstract 586: Withaferin-A inhibits prostate tumor growth by enhancing anti-tumor immune response

Abstract

Abstract Indolent nature of prostate cancer provides a ‘large window’ of opportunity for chemopreventive strategies. Most chemopreventive strategies are primarily focused on controlling and/or reversing the mechanisms involved in neoplastic transformation and cancer progression. It is now well accepted that tumors evade the patient's defense system during progression and growth at distant sites. Mounting evidences suggest immunological defects in prostate cancer patients with higher numbers of functionally suppressive CD4+CD25+FOXP3+ T cells (Treg) and lower number of effectors T cells. Furthermore, tumor microenvironment exerts a profound immunosuppressive effect on effectors T cells by secreting TGF-β and IL-10. Therefore, modulating TGF-β and IL-10 using natural and dietary components constitutes an innovative approach for prostate cancer prevention and treatment. In this study, we have shown that Withaferin-A (WA), a bioactive compound isolated from Withania Somnifera also called “Ashwagandha” has the ability to modulate immunosuppressive cytokines (IL-10 and TGF-β) produced by the prostate cancer cells. Additionally, we show selective inhibition of Treg proliferation and induction of apoptosis in Tregs cells in immune competent prostate cancer mouse model treated with WA compared to controls. Our results suggest that WA have potential to fine-tune immunosuppressive phenotype of tumor-associated lymphocytes by modulating immuno-suppressive cytokines. Significant inhibition of tumor growth in immune competent prostate cancer mouse model as compared to immune deficient xenograft suggest potential role of WA on reversal of anti-tumor immune response from immune suppression to immune competence, which is required to fight against prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 586. doi:1538-7445.AM2012-586