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1.
J Proteomics ; 206: 103447, 2019 08 30.
Article in English | MEDLINE | ID: mdl-31326558

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.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Benzoxepins/pharmacology , Limonins/pharmacology , Metabolic Networks and Pathways/drug effects , Metabolome/drug effects , Prostatic Neoplasms/metabolism , Antineoplastic Agents, Phytogenic/therapeutic use , Apoptosis/drug effects , Cell Proliferation/drug effects , Humans , Male , Metabolomics/methods , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Tumor Cells, Cultured
2.
J Chromatogr B Analyt Technol Biomed Life Sci ; 1102-1103: 143-151, 2018 Dec 01.
Article in English | MEDLINE | ID: mdl-30391728

ABSTRACT

Prostate cancer is known as a common malignant tumor in clinics and moreover, traditional chemotherapeutic drugs have great toxic side effects and drug resistance. Therefore, the searching the highly efficient and low toxicity antitumor drugs from natural drugs has become an important approach for the treatment of prostate cancer. Many studies showed that Cortex Phellodendri has important therapeutic significance for prostate cancer. Magnoline is the main component of Cortex Phellodendri Amurensis, and it is of great significance to evaluate the effect of magnoline on prostate cancer. By using metabolomics, we established a comprehensive analysis strategy based on cell metabolic analysis to study the inhibitory effect of magnoline on the proliferation of prostate cancer cell line 22RV1, and finally conducted an analysis on the cell metabolism footprint samples. Results showed that magnoline had a significant inhibitory effect on the proliferation of the prostate cancer cell line 22RV1. According to the established cell metabolomics methods, we found that 12 metabolic biomarkers of the cell metabolic footprint samples, respectively, could inhibit the proliferation of prostate cancer cells. Magnoline could significantly affect these metabolic biomarkers to disrupt the growth and proliferation of the prostate cancer cell line 22RV1. Additionally, through MetPA analysis indicated that these biomarkers were closely correlated with a variety of metabolic pathways in tumor cells, including the energy metabolism, amino acid metabolism and fatty acid metabolism, most of which were associated with nutrition and energy metabolism. Therefore, we speculated that because of the disturbance of nutrition metabolism and energy metabolism of the prostate cancer cell line 22RV1, cells could not provide the material basis for rapid proliferation, eventually resulting in the inhibition effect.


Subject(s)
Isoquinolines/metabolism , Metabolome/drug effects , Prostatic Neoplasms/metabolism , Signal Transduction/drug effects , Cell Line, Tumor , Chromatography, High Pressure Liquid , Humans , Isoquinolines/pharmacology , Male , Mass Spectrometry , Metabolomics/methods
3.
Sci Rep ; 7: 46234, 2017 04 06.
Article in English | MEDLINE | ID: mdl-28383015

ABSTRACT

Screening the active compounds of herbal medicines is of importance to modern drug discovery. In this work, an integrative strategy was established to discover the effective compounds and their therapeutic targets using Phellodendri Amurensis cortex (PAC) aimed at inhibiting prostate cancer as a case study. We found that PAC could be inhibited the growth of xenograft tumours of prostate cancer. Global constituents and serum metabolites were analysed by UPLC-MS based on the established chinmedomics analysis method, a total of 54 peaks in the spectrum of PAC were characterised in vitro and 38 peaks were characterised in vivo. Among the 38 compounds characterised in vivo, 29 prototype components were absorbed in serum and nine metabolites were identified in vivo. Thirty-four metabolic biomarkers were related to prostate cancer, and PAC could observably reverse these metabolic biomarkers to their normal level and regulate the disturbed metabolic profile to a healthy state. A chinmedomics approach showed that ten absorbed constituents, as effective compounds, were associated with the therapeutic effect of PAC. In combination with bioactivity assays, the action targets were also predicted and discovered. As an illustrative case study, the strategy was successfully applied to high-throughput screening of active compounds from herbal medicine.


Subject(s)
Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/therapeutic use , Prostatic Neoplasms/drug therapy , Animals , Carcinogenesis/drug effects , Carcinogenesis/pathology , Cell Proliferation/drug effects , Drugs, Chinese Herbal/pharmacology , High-Throughput Screening Assays , Humans , Male , Metabolic Networks and Pathways , Metabolomics , Mice , Mice, Inbred BALB C , Mice, Nude , Multivariate Analysis , Prostatic Neoplasms/pathology
4.
J Sep Sci ; 39(24): 4700-4711, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27778479

ABSTRACT

Zi Shen Wan is a typical formula consisting of three herbs, Phellodendri Amurensis Cortex, Rhizoma Anemarrhenae, and Cortex Cinnamomi, and has been widely used for treating prostatitis and infection diseases. However, it lacks in-depth research of the constituents of Zi Shen Wan in vivo and in vitro. In this work, ultra high performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry and MassLynx software was established to characterize the chemical compositions of Zi Shen Wan in vivo and in vitro. In total, 92 peaks were characterized in vitro and 33 peaks were characterized in vivo based on mass spectrometry and tandem mass spectrometry data. Among the 33 compounds characterized in rat plasma, 22 prototype components absorbed in rat serum and 11 metabolites were identified in vivo. This work was fully reports the chemical constituents of traditional Chinese formula of Zi Shen Wan, it demonstrated that ultra high performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry coupled to MassLynx software and multivariate data processing approach could be successfully applied for rapid screening and comprehensive analysis of chemical constituents in vitro and prototype components or metabolites in vivo of traditional Chinese medicine.


Subject(s)
Drugs, Chinese Herbal/chemistry , Phytochemicals/blood , Administration, Oral , Animals , Chromatography, High Pressure Liquid , Male , Multivariate Analysis , Phytochemicals/pharmacokinetics , Rats , Tandem Mass Spectrometry
5.
Chin J Nat Med ; 13(9): 687-98, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26412429

ABSTRACT

Chuanwu (CW), a famous traditional Chinese medicine (TCM) from the mother roots of Aconitum carmichaelii Debx.. (Ranunculaceae), has been used for the treatment of various diseases. Unfortunately, its toxicity is frequently reported because of its narrow therapeutic window. In the present study, a metabolomic method was performed to characterize the phenotypically biochemical perturbations and potential mechanisms of CW-induced toxicity. Meanwhile, the expression level of toxicity biomarkers in the urine were analyzed to evaluate the detoxification by combination with Gancao (Radix Glyeyrrhizae, CG), Baishao (Radix Paeoniae Alba, CS) and Ganjiang (Rhizoma Zingiberis, CJ), which were screened from classical TCM prescriptions. Urinary metabolomics was performed by UPLC-Q-TOF-HDMS, and the mass spectra signals of the detected metabolites were systematically analyzed using pattern recognition methods. As a result, seventeen biomarkers associated with CW toxicity were identified, which were associated with pentose and glucuronate interconversions, alanine, aspartate, and glutamate metabolism, among others. The expression levels of most toxicity biomarkers were effectively modulated towards the normal range by the compatibility drugs. It indicated that the three compatibility drugs could effectively detoxify CW. In summary, our work demonstrated that metabolomics was vitally significant to evaluation of toxicity and finding detoxification methods for TCM.


Subject(s)
Aconitum/toxicity , Drug-Related Side Effects and Adverse Reactions/metabolism , Drugs, Chinese Herbal , Glycyrrhiza uralensis , Metabolome , Paeonia , Zingiber officinale , Animals , Biomarkers/urine , Chromatography, High Pressure Liquid/methods , Drug-Related Side Effects and Adverse Reactions/prevention & control , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use , Drugs, Chinese Herbal/toxicity , Heart , Inactivation, Metabolic , Liver , Male , Mass Spectrometry/methods , Medicine, Chinese Traditional , Metabolomics , Plant Roots , Rats, Wistar , Rhizome
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