Triterpenoid ursolic acid drives metabolic rewiring and epigenetic reprogramming in treatment/prevention of human prostate cancer

• DOI: 10.1002/mc.23365
• Publication Date: 2021-11-02T21:48:45Z
• Authors: Shanyi Li; Renyi Wu; Lujing Wang; Hsiao‐Chen Dina Kuo; Davit Sargsyan; Xi Zheng; Yujue Wang; Xiaoyang Su; Ah‐Ng Kong
• Keywords: Reprogramming; Epigenomics; DNA demethylation; Differentially methylated regions

Ursolic acid (UA) is a triterpenoid phytochemical with strong anticancer effect. The metabolic rewiring, epigenetic reprogramming, and chemopreventive effect of UA in prostate cancer (PCa) remain unknown. Herein, we investigated the efficacy PCa xenograft, its biological effects on cellular metabolism, DNA methylation, transcriptomic using multi-omics approaches. metabolomics was quantified by liquid-chromatography-mass spectrometry (LC-MS) while epigenomic CpG methylation parallel gene expression studied next-generation sequencing technologies. administration attenuated growth transplanted human VCaP-Luc cells immunodeficient mice. regulated several metabolites metabolism-related signaling pathways including S-adenosylmethionine (SAM), methionine, glucose 6-phosphate, CDP-choline, phosphatidylcholine biosynthesis, glycolysis, nucleotide sugars metabolism. RNA-seq analyses revealed pathways, CXCR4 signaling, metastasis NRF2-mediated oxidative stress response. Epigenetic reprogramming study Methyl-seq uncovered list differentially methylated regions (DMRs) associated treatment. Transcriptome-DNA methylome correlative analysis genes, which changes correlated promoter status. Altogether, our results suggest that regulates rewiring metabolism SAM potentially driving resulting overall