Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II
<b>Background/Objectives:</b> Incomptine A (IA) has cytotoxic activity in non-Hodgkin lymphoma (NHL) cancer cell lines. Its effects on U-937 cells include induction of apoptosis, production of reactive oxygen species, and inhibition of glycolytic enzymes. We examined the altered protein...
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2025-02-01
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| author | Normand García-Hernández Fernando Calzada Elihú Bautista José Manuel Sánchez-López Miguel Valdes Marta Elena Hernández-Caballero Rosa María Ordoñez-Razo |
| author_facet | Normand García-Hernández Fernando Calzada Elihú Bautista José Manuel Sánchez-López Miguel Valdes Marta Elena Hernández-Caballero Rosa María Ordoñez-Razo |
| author_sort | Normand García-Hernández |
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| description | <b>Background/Objectives:</b> Incomptine A (IA) has cytotoxic activity in non-Hodgkin lymphoma (NHL) cancer cell lines. Its effects on U-937 cells include induction of apoptosis, production of reactive oxygen species, and inhibition of glycolytic enzymes. We examined the altered protein levels present in the lymph nodes of an in vivo mouse model. <b>Methods:</b> We induced an in vivo model with Balb/c mice with U-937 cells and treated it with IA or methotrexate, as well as healthy mice. We determined expressed proteins by TMT based on the LC-MS/MS method (Data are available via ProteomeXchange with identifier PXD060392) and a molecular docking study targeting 15 deregulated proteins. We developed analyses through the KEGG, Reactome, and Gene Ontology databases. <b>Results:</b> A total of 2717 proteins from the axillary and inguinal lymph nodes were analyzed and compared with healthy mice. Of 412 differentially expressed proteins, 132 were overexpressed (FC ≥ 1.5) and 117 were underexpressed (FC ≤ 0.67). This altered expression was associated with 20 significantly enriched processes, including chromatin remodeling, transcription, translation, metabolic and energetic processes, oxidative phosphorylation, glycolysis/gluconeogenesis, cell proliferation, cytoskeletal organization, and with cell death with necroptosis. <b>Conclusions:</b> We confirmed the previously observed dose-dependent effect of IA as a secondary metabolite with important potential as an anticancer agent for the treatment of NHL, showing that the type of drug or the anatomical location influences the response to treatment. The IA promises to be a likely safer and more effective treatment to improve outcomes, reduce toxicities, and improve survival in patients with NHL, initially targeting histones and transcription factors that will affect cell death proteins. |
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| institution | OA Journals |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-02-01 |
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| series | Pharmaceuticals |
| spelling | doaj-art-7fd41654baaa4abd9700ef1dc9c4adf92025-08-20T02:03:27ZengMDPI AGPharmaceuticals1424-82472025-02-0118224210.3390/ph18020242Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part IINormand García-Hernández0Fernando Calzada1Elihú Bautista2José Manuel Sánchez-López3Miguel Valdes4Marta Elena Hernández-Caballero5Rosa María Ordoñez-Razo6Unidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría 2° Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, MexicoUnidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, 2° Piso CORSE, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, MexicoSECIHTI-División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica A.C., San Luis Potosí 78216, San Luis Potosí, MexicoHospital Infantil de Tlaxcala, Investigación y Enseñanza, 20 de Noviembre S/M, San Matias Tepetomatitlan, Apetatitlan de de Antonio Carvajal 90606, Tlaxcala, MexicoUnidad de Investigación Médica en Farmacología, UMAE Hospital de Especialidades, 2° Piso CORSE, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, MexicoFacultad de Medicina, Biomedicina, Benemérita Universidad Autónoma de Puebla, Puebla 72410, Puebla, MexicoUnidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría 2° Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, Mexico<b>Background/Objectives:</b> Incomptine A (IA) has cytotoxic activity in non-Hodgkin lymphoma (NHL) cancer cell lines. Its effects on U-937 cells include induction of apoptosis, production of reactive oxygen species, and inhibition of glycolytic enzymes. We examined the altered protein levels present in the lymph nodes of an in vivo mouse model. <b>Methods:</b> We induced an in vivo model with Balb/c mice with U-937 cells and treated it with IA or methotrexate, as well as healthy mice. We determined expressed proteins by TMT based on the LC-MS/MS method (Data are available via ProteomeXchange with identifier PXD060392) and a molecular docking study targeting 15 deregulated proteins. We developed analyses through the KEGG, Reactome, and Gene Ontology databases. <b>Results:</b> A total of 2717 proteins from the axillary and inguinal lymph nodes were analyzed and compared with healthy mice. Of 412 differentially expressed proteins, 132 were overexpressed (FC ≥ 1.5) and 117 were underexpressed (FC ≤ 0.67). This altered expression was associated with 20 significantly enriched processes, including chromatin remodeling, transcription, translation, metabolic and energetic processes, oxidative phosphorylation, glycolysis/gluconeogenesis, cell proliferation, cytoskeletal organization, and with cell death with necroptosis. <b>Conclusions:</b> We confirmed the previously observed dose-dependent effect of IA as a secondary metabolite with important potential as an anticancer agent for the treatment of NHL, showing that the type of drug or the anatomical location influences the response to treatment. The IA promises to be a likely safer and more effective treatment to improve outcomes, reduce toxicities, and improve survival in patients with NHL, initially targeting histones and transcription factors that will affect cell death proteins.https://www.mdpi.com/1424-8247/18/2/242incomptine Anon-Hodgkin lymphomaproteome TMT-basedmolecular dockingnecroptosis |
| spellingShingle | Normand García-Hernández Fernando Calzada Elihú Bautista José Manuel Sánchez-López Miguel Valdes Marta Elena Hernández-Caballero Rosa María Ordoñez-Razo Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II Pharmaceuticals incomptine A non-Hodgkin lymphoma proteome TMT-based molecular docking necroptosis |
| title | Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II |
| title_full | Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II |
| title_fullStr | Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II |
| title_full_unstemmed | Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II |
| title_short | Quantitative Proteomics and Molecular Mechanisms of Non-Hodgkin Lymphoma Mice Treated with Incomptine A, Part II |
| title_sort | quantitative proteomics and molecular mechanisms of non hodgkin lymphoma mice treated with incomptine a part ii |
| topic | incomptine A non-Hodgkin lymphoma proteome TMT-based molecular docking necroptosis |
| url | https://www.mdpi.com/1424-8247/18/2/242 |
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