Abstract 4713: Extraction, purification and evaluation of prmt5-inhibitory phytochemical compounds for the treatment of prostate adenocarcinoma

Abstract

Abstract The development and advancement of prostate cancer is supported by a plethora of genetic and proteomic abnormalities, including events of post-translational modifications. The protein arginine methyltransferase 5 (PRMT5) enzyme regulates epigenetic events of histone modifications and of post-translational modifications within protein signaling pathways. Under abnormal conditions of overexpression and/or upregulation, PRMT5 functions by constitutively driving the growth and/or proliferation of dysregulated cells. Overexpression and/or upregulation of PRMT5 correlates with disease progression as observed among numerous cancer types, including breast, colorectal, leukemia, lung, melanoma and prostate cancers. We demonstrated previously that PRMT5 localized to the cytoplasm, functions to drive both growth and proliferation of prostatic tumors. Plants naturally produce chemical toxins as mechanisms of defense against microbial and other biological threats. Human exploitation, consumption and/or application of agents isolated from plants for therapeutic intervention dates back throughout the millennia. In this study, we extracted, purified and evaluated natural, small, chemical compounds from plant products that antagonize PRMT5 activity in prostate cancer cells. We found that crude and purified extracts of Dendrobium, Fennel Seed and Magnolia plants attenuated prostate tumor growth and proliferation by selective inhibition of PRMT5 methyltransferase activity. These findings establish the first set of natural PRMT5-specific inhibitors reported. Citation Format: Oliver H. Richmond, Zhengxin Wang. Extraction, purification and evaluation of prmt5-inhibitory phytochemical compounds for the treatment of prostate adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4713.