Identification of the perturbed metabolic pathways associating with prostate cancer cells and anticancer affects of obacunone

Abstract

Functional metabolomics could bring correlative information about specific cell types under different conditions for exploring cell properties and functions. In this study, we adopt a non-targeted cell metabolomics strategy to reveal the proliferation inhibition mechanism of obacunone on 22RV1 prostate cancer cells. Using high-throughput liquid chromatography-high definition mass spectrometry combined with pattern recognition methods was performed to analyze the cell metabolic profiles and pathway of obacunone on prostate cancer. A total of twenty one proposed metabolites in prostate cancer cell and nine vital metabolic pathways such as nicotinate and nicotinamide metabolism, phenylalanine metabolism as well as tryptophan metabolism were identified from large amounts of data. Then, we have built an overall metabolic description network of obacunone to defense prostate cancer. In addition, morphological observation, cell proliferation and apoptosis analysis of 22RV1 human prostate cancer cells were performed to better understand physiopathologic changes after obacunone treatment. Functional metabolomics is a valuable tool that insight into the natural product mechanisms and contributes to new drug discovery. SIGNIFICANCE: In this study, we probe into the proliferation inhibition effect of obacunone on 22RV1 prostate cancer cells by differentiating metabolic changes of cell sample in control and obacunone administration. Using the non-targeted and targeted cell metabolomics approaches, our findings were manifested that obacunone effectually control proliferation and promote apoptosis in 22RV1 prostate cancer cells, which were related to twenty one proposed metabolites, and nicotinate and nicotinamide metabolism, phenylalanine metabolism, tryptophan metabolism as well as ascorbate metabolism. These data were suggested that functional metabolomics analysis have potential to explore the pharmacodynamic mechanism through resolving metabolic changes in cancer cells that possesses higher clinical application value. The advances in the molecular understanding of the roles of metabolomic pathway concerned with particular metabolites in obacunone administration attract more attention in favor of burgeoning therapeutic measures resisting prostate cancer.

Keywords: Metabolic pathway; Metabolites; Metabolomics; Obacunone; Prostate cancer.