Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part I
<b>Background</b>: Incomptine A (<b>IA</b>) has been reported to have cytotoxic activity in non-Hodgkin lymphoma cancer cell lines and have effects on U-937 cells, including the induction of apoptosis, the production of reactive oxygen species, and the inhibition of glycolyti...
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2024-12-01
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| Online Access: | https://www.mdpi.com/1424-8247/18/1/5 |
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| author | Fernando Calzada Normand García-Hernández Elihú Bautista José Manuel Sánchez-López Miguel Valdes Claudia Velázquez Elizabeth Barbosa |
| author_facet | Fernando Calzada Normand García-Hernández Elihú Bautista José Manuel Sánchez-López Miguel Valdes Claudia Velázquez Elizabeth Barbosa |
| author_sort | Fernando Calzada |
| collection | DOAJ |
| description | <b>Background</b>: Incomptine A (<b>IA</b>) has been reported to have cytotoxic activity in non-Hodgkin lymphoma cancer cell lines and have effects on U-937 cells, including the induction of apoptosis, the production of reactive oxygen species, and the inhibition of glycolytic enzymes. Also, <b>IA</b> has cytotoxic activity in the triple-negative subtypes, HER2+, and luminal A of breast cancer cells, with its properties being associated with an effect on the antiapoptotic function of Hexokinase II (HKII). <b>Objectives</b>: In this research, we reviewed the altered levels of proteins present in the lymph nodes of male Balb/c mice inoculated with U-937 cells and treated with <b>IA</b> or methotrexate, as well as mice only inoculated with cancer cells. <b>Methods</b>: Five approaches, including Tandem Mass Tag (TMT), Gene ontology (GO), Reactome, KEGG pathway analysis, and molecular docking, were used. <b>Results</b>: TMT showed that 74 proteins were differentially expressed, out of which 12 presented overexpression (FC ≥ 1.5) and 62 were under expressed (FC ≤ 0.67). In general, the TMT approach showed that <b>IA</b> had a better effect on proteins than methotrexate. Gene ontology, Reactome, and KEGG pathway analysis showed that proteins with altered levels may be implicated in several processes, including gene silencing by RNA, oxidative phosphorylation, glycolysis/gluconeogenesis, cytoskeleton organization, and ATP metabolic and energetic processes. The molecular docking analysis, which used 23 altered proteins as targets, revealed that <b>IA</b> interacted with all the proteins used. <b>Conclusions</b>: The results obtained using the five bioinformatic approaches provide information and show that <b>IA</b> could be used to treat non-Hodgkin lymphoma induced with the U-937 cell line. Also, it could provide a basis for future research and the development of clinical trials. |
| format | Article |
| id | doaj-art-8118230c2b424bac8a8d158d78196d2d |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | MDPI AG |
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| series | Pharmaceuticals |
| spelling | doaj-art-8118230c2b424bac8a8d158d78196d2d2025-01-24T13:44:57ZengMDPI AGPharmaceuticals1424-82472024-12-01181510.3390/ph18010005Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part IFernando Calzada0Normand García-Hernández1Elihú Bautista2José Manuel Sánchez-López3Miguel Valdes4Claudia Velázquez5Elizabeth Barbosa6Unidad 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, MexicoUnidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría 2º Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, MexicoCONAHCYT-División de Biología Molecular, Instituto Potosino de Investigación Científica y Tecnológica A. C, San Luis Potosí 78216, MexicoUnidad de Investigación Médica en Genética Humana, UMAE Hospital Pediatría 2º Piso, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Av. Cuauhtémoc 330, Col. Doctores, Mexico City 06725, MexicoInstituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Plan de San Luis y Salvador Díaz Mirón S/N, Col. Casco de Santo Tomás, Miguel Hidalgo, Mexico City 11340, MexicoÁrea Académica de Farmacia, Instituto de Ciencias de la Salud, Universidad Autonoma del Estado de Hidalgo, Circuito exHacienda La Concepción S/N, Carretera Pachuca-Atocpan, San Agustin Tlaxiaca 42076, MexicoInstituto Politécnico Nacional, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Plan de San Luis y Salvador Díaz Mirón S/N, Col. Casco de Santo Tomás, Miguel Hidalgo, Mexico City 11340, Mexico<b>Background</b>: Incomptine A (<b>IA</b>) has been reported to have cytotoxic activity in non-Hodgkin lymphoma cancer cell lines and have effects on U-937 cells, including the induction of apoptosis, the production of reactive oxygen species, and the inhibition of glycolytic enzymes. Also, <b>IA</b> has cytotoxic activity in the triple-negative subtypes, HER2+, and luminal A of breast cancer cells, with its properties being associated with an effect on the antiapoptotic function of Hexokinase II (HKII). <b>Objectives</b>: In this research, we reviewed the altered levels of proteins present in the lymph nodes of male Balb/c mice inoculated with U-937 cells and treated with <b>IA</b> or methotrexate, as well as mice only inoculated with cancer cells. <b>Methods</b>: Five approaches, including Tandem Mass Tag (TMT), Gene ontology (GO), Reactome, KEGG pathway analysis, and molecular docking, were used. <b>Results</b>: TMT showed that 74 proteins were differentially expressed, out of which 12 presented overexpression (FC ≥ 1.5) and 62 were under expressed (FC ≤ 0.67). In general, the TMT approach showed that <b>IA</b> had a better effect on proteins than methotrexate. Gene ontology, Reactome, and KEGG pathway analysis showed that proteins with altered levels may be implicated in several processes, including gene silencing by RNA, oxidative phosphorylation, glycolysis/gluconeogenesis, cytoskeleton organization, and ATP metabolic and energetic processes. The molecular docking analysis, which used 23 altered proteins as targets, revealed that <b>IA</b> interacted with all the proteins used. <b>Conclusions</b>: The results obtained using the five bioinformatic approaches provide information and show that <b>IA</b> could be used to treat non-Hodgkin lymphoma induced with the U-937 cell line. Also, it could provide a basis for future research and the development of clinical trials.https://www.mdpi.com/1424-8247/18/1/5incomptine Asesquiterpene lactone<i>Decachaeta incompta</i>cancernon-Hodgkin lymphomaTMT |
| spellingShingle | Fernando Calzada Normand García-Hernández Elihú Bautista José Manuel Sánchez-López Miguel Valdes Claudia Velázquez Elizabeth Barbosa Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part I Pharmaceuticals incomptine A sesquiterpene lactone <i>Decachaeta incompta</i> cancer non-Hodgkin lymphoma TMT |
| title | Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part I |
| title_full | Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part I |
| title_fullStr | Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part I |
| title_full_unstemmed | Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part I |
| title_short | Understanding the Molecular Mechanisms of Incomptine A in Treating Non-Hodgkin Lymphoma Associated with U-937 Cells: Bioinformatics Approaches, Part I |
| title_sort | understanding the molecular mechanisms of incomptine a in treating non hodgkin lymphoma associated with u 937 cells bioinformatics approaches part i |
| topic | incomptine A sesquiterpene lactone <i>Decachaeta incompta</i> cancer non-Hodgkin lymphoma TMT |
| url | https://www.mdpi.com/1424-8247/18/1/5 |
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