An untargeted UPLC-Q-TOF-MS-based plasma metabonomics revealed the effects of peperomin E in a prostate cancer nude mouse model

Peperomia dindygulensis is used as an anticancer medicinal plant in China and is rich in a series of novel secolignans, including peperomin E (PE). In our prior study, we demonstrated the significant reduction in tumor weight and volume in vivo in a PCa DU145 cell xenograft tumor mouse model following PE treatment. However, the impact of PE on PCa metabolism remains unclear. Therefore, the objective of this investigation is to examine the influence of PE on metabolism regulation within a PCa mouse model. An untargeted UPLC-Q-TOF-MS plasma metabolomics approach was carried out to explore the mechanism of action of PE in a human prostate cancer DU145 cell xenograft tumour mouse model based on principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), identification of potential biomarkers and pathway analysis. A total of 71 potential plasma metabolite biomarkers were identified in the nude mouse model and 36 of which were reversed to different degrees after the treatment with PE. These identified biomarkers primarily relate to amino acid metabolism, fatty acid metabolism and cholic acid metabolism. These findings showed that PE could improve endogenous metabolism in the DU145 cell xenograft tumor mouse model and offered a reliable foundation for the design of new therapeutic drugs for treating PCa.