Serum Starvation Enhances the Antitumor Activity of Natural Matrices: Insights into Bioactive Molecules from Dromedary Urine Extracts

Natural matrices have historically been a cornerstone in drug discovery, offering a rich source of structurally diverse and biologically active compounds. However, research on natural products often faces significant challenges due to the complexity of natural matrices, such as urine, and the limita...

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Main Authors: Maria Noemi Sgobba, Biagia Musio, Carlos Iglesias Pastrana, Stefano Todisco, Nikola Schlosserovà, Federica Mastropirro, Maria Favia, Antonio Radesco, Iola F. Duarte, Anna De Grassi, Mariateresa Volpicella, Vito Gallo, Ciro Leonardo Pierri, Elena Ciani, Lorenzo Guerra
Format: Article
Language:English
Published: MDPI AG 2025-02-01
Series:Molecules
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Online Access:https://www.mdpi.com/1420-3049/30/4/821
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author Maria Noemi Sgobba
Biagia Musio
Carlos Iglesias Pastrana
Stefano Todisco
Nikola Schlosserovà
Federica Mastropirro
Maria Favia
Antonio Radesco
Iola F. Duarte
Anna De Grassi
Mariateresa Volpicella
Vito Gallo
Ciro Leonardo Pierri
Elena Ciani
Lorenzo Guerra
author_facet Maria Noemi Sgobba
Biagia Musio
Carlos Iglesias Pastrana
Stefano Todisco
Nikola Schlosserovà
Federica Mastropirro
Maria Favia
Antonio Radesco
Iola F. Duarte
Anna De Grassi
Mariateresa Volpicella
Vito Gallo
Ciro Leonardo Pierri
Elena Ciani
Lorenzo Guerra
author_sort Maria Noemi Sgobba
collection DOAJ
description Natural matrices have historically been a cornerstone in drug discovery, offering a rich source of structurally diverse and biologically active compounds. However, research on natural products often faces significant challenges due to the complexity of natural matrices, such as urine, and the limitations of bioactivity assessment assays. To ensure reliable insights, it is crucial to optimize experimental conditions to reveal the bioactive potential of samples, thereby improving the validity of statistical analyses. Approaches in metabolomics further strengthen this process by identifying and focusing on the most promising compounds within natural matrices, enhancing the precision of bioactive metabolite prioritization. In this study, we assessed the bioactivity of 17 dromedary urine samples on human renal cells under serum-reduced conditions (1%FBS) in order to minimize possible FBS-derived interfering factors. Using viability assays and Annexin V/PI staining, we found that the tumor renal cell lines Caki-1 and RCC-Shaw were more sensitive to the cytotoxic effects of the small molecules present in dromedary urine compared to non-tumor HK-2 cells. Employing NMR metabolomics analysis combined with detected in vitro activity, our statistical model highlights the presence of bioactive compounds in dromedary urine, such as azelaic acid and phenylacetyl glycine, underscoring its potential as a sustainable source of bioactive molecules within the framework of green chemistry and circular economy initiatives.
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spelling doaj-art-a466f6a4b5e94c7788c96f2d542f2dfa2025-08-20T02:44:35ZengMDPI AGMolecules1420-30492025-02-0130482110.3390/molecules30040821Serum Starvation Enhances the Antitumor Activity of Natural Matrices: Insights into Bioactive Molecules from Dromedary Urine ExtractsMaria Noemi Sgobba0Biagia Musio1Carlos Iglesias Pastrana2Stefano Todisco3Nikola Schlosserovà4Federica Mastropirro5Maria Favia6Antonio Radesco7Iola F. Duarte8Anna De Grassi9Mariateresa Volpicella10Vito Gallo11Ciro Leonardo Pierri12Elena Ciani13Lorenzo Guerra14Department of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, ItalyDepartment of Civil, Environmental, Land, Building Engineering and Chemistry (DICATECh), Polytechnic University of Bari, Via Orabona 4, 70125 Bari, ItalyFaculty of Veterinary Sciences, Department of Genetics, University of Córdoba, 14071 Córdoba, SpainDepartment of Civil, Environmental, Land, Building Engineering and Chemistry (DICATECh), Polytechnic University of Bari, Via Orabona 4, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, ItalyDepartment of Translational Biomedicine and Neurosciences (DiBraiN), University of Bari “Aldo Moro”, Piazza Giulio Cesare, 70124 Bari, ItalyIstituto Tumori “Giovanni Paolo II” I.R.C.C.S., Viale Orazio Flacco 65, 70124 Bari, ItalyDepartment of Chemistry, CICECO—Aveiro Institute of Materials and LAQV-REQUIMTE, University of Aveiro, 3810-193 Aveiro, PortugalDepartment of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, ItalyDepartment of Civil, Environmental, Land, Building Engineering and Chemistry (DICATECh), Polytechnic University of Bari, Via Orabona 4, 70125 Bari, ItalyDepartment of Pharmacy—Pharmaceutical Sciences, University of Bari Aldo Moro, Via Orabona 4, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, ItalyDepartment of Biosciences, Biotechnologies and Environment, University of Bari “Aldo Moro”, Via Orabona 4, 70125 Bari, ItalyNatural matrices have historically been a cornerstone in drug discovery, offering a rich source of structurally diverse and biologically active compounds. However, research on natural products often faces significant challenges due to the complexity of natural matrices, such as urine, and the limitations of bioactivity assessment assays. To ensure reliable insights, it is crucial to optimize experimental conditions to reveal the bioactive potential of samples, thereby improving the validity of statistical analyses. Approaches in metabolomics further strengthen this process by identifying and focusing on the most promising compounds within natural matrices, enhancing the precision of bioactive metabolite prioritization. In this study, we assessed the bioactivity of 17 dromedary urine samples on human renal cells under serum-reduced conditions (1%FBS) in order to minimize possible FBS-derived interfering factors. Using viability assays and Annexin V/PI staining, we found that the tumor renal cell lines Caki-1 and RCC-Shaw were more sensitive to the cytotoxic effects of the small molecules present in dromedary urine compared to non-tumor HK-2 cells. Employing NMR metabolomics analysis combined with detected in vitro activity, our statistical model highlights the presence of bioactive compounds in dromedary urine, such as azelaic acid and phenylacetyl glycine, underscoring its potential as a sustainable source of bioactive molecules within the framework of green chemistry and circular economy initiatives.https://www.mdpi.com/1420-3049/30/4/821natural matricesdromedary urine extractsserum-reduced conditionshuman renal cellscell viabilityapoptosis
spellingShingle Maria Noemi Sgobba
Biagia Musio
Carlos Iglesias Pastrana
Stefano Todisco
Nikola Schlosserovà
Federica Mastropirro
Maria Favia
Antonio Radesco
Iola F. Duarte
Anna De Grassi
Mariateresa Volpicella
Vito Gallo
Ciro Leonardo Pierri
Elena Ciani
Lorenzo Guerra
Serum Starvation Enhances the Antitumor Activity of Natural Matrices: Insights into Bioactive Molecules from Dromedary Urine Extracts
Molecules
natural matrices
dromedary urine extracts
serum-reduced conditions
human renal cells
cell viability
apoptosis
title Serum Starvation Enhances the Antitumor Activity of Natural Matrices: Insights into Bioactive Molecules from Dromedary Urine Extracts
title_full Serum Starvation Enhances the Antitumor Activity of Natural Matrices: Insights into Bioactive Molecules from Dromedary Urine Extracts
title_fullStr Serum Starvation Enhances the Antitumor Activity of Natural Matrices: Insights into Bioactive Molecules from Dromedary Urine Extracts
title_full_unstemmed Serum Starvation Enhances the Antitumor Activity of Natural Matrices: Insights into Bioactive Molecules from Dromedary Urine Extracts
title_short Serum Starvation Enhances the Antitumor Activity of Natural Matrices: Insights into Bioactive Molecules from Dromedary Urine Extracts
title_sort serum starvation enhances the antitumor activity of natural matrices insights into bioactive molecules from dromedary urine extracts
topic natural matrices
dromedary urine extracts
serum-reduced conditions
human renal cells
cell viability
apoptosis
url https://www.mdpi.com/1420-3049/30/4/821
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