Untargeted LC-MS/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell Lines
Breast cancer (BC) is one of the biggest health problems worldwide, characterized by intricate metabolic and biochemical complexities stemming from pronounced variations across dysregulated molecular pathways. If BC is not diagnosed early, complications may lead to death. Thus, the pursuit of novel...
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/19/14543 |
| _version_ | 1797575852673728512 |
|---|---|
| author | Alan Rubén Estrada-Pérez Juan Benjamín García-Vázquez Humberto L. Mendoza-Figueroa Martha Cecilia Rosales-Hernández Cynthia Fernández-Pomares José Correa-Basurto |
| author_facet | Alan Rubén Estrada-Pérez Juan Benjamín García-Vázquez Humberto L. Mendoza-Figueroa Martha Cecilia Rosales-Hernández Cynthia Fernández-Pomares José Correa-Basurto |
| author_sort | Alan Rubén Estrada-Pérez |
| collection | DOAJ |
| description | Breast cancer (BC) is one of the biggest health problems worldwide, characterized by intricate metabolic and biochemical complexities stemming from pronounced variations across dysregulated molecular pathways. If BC is not diagnosed early, complications may lead to death. Thus, the pursuit of novel therapeutic avenues persists, notably focusing on epigenetic pathways such as histone deacetylases (HDACs). The compound <i>N</i>-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), a derivative of valproic acid (VPA), has emerged as a promising candidate warranting pre-clinical investigation. HO-AAVPA is an HDAC inhibitor with antiproliferative effects on BC, but its molecular mechanism has yet to be deciphered. Furthermore, in the present study, we determined the metabolomic effects of HO-AAVPA and VPA on cells of luminal breast cancer (MCF-7) and triple-negative breast cancer (MDA-MB-231) subtypes. The LC-MS untargeted metabolomic study allowed for the simultaneous measurement of multiple metabolites and pathways, identifying that both compounds affect glycerophospholipid and sphingolipid metabolism in the MCF-7 and MDA-MB-231 cell lines, suggesting that other biological targets were different from HDACs. In addition, there are different dysregulate metabolites, possibly due to the physicochemical differences between HO-AAVPA and VPA. |
| first_indexed | 2024-03-10T21:44:09Z |
| format | Article |
| id | doaj.art-e1ffe9086538443bbf05894358469c80 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:44:09Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-e1ffe9086538443bbf05894358469c802023-11-19T14:28:09ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191454310.3390/ijms241914543Untargeted LC-MS/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell LinesAlan Rubén Estrada-Pérez0Juan Benjamín García-Vázquez1Humberto L. Mendoza-Figueroa2Martha Cecilia Rosales-Hernández3Cynthia Fernández-Pomares4José Correa-Basurto5Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, MexicoLaboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, MexicoLaboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, MexicoLaboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, MexicoLaboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, MexicoLaboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, MexicoBreast cancer (BC) is one of the biggest health problems worldwide, characterized by intricate metabolic and biochemical complexities stemming from pronounced variations across dysregulated molecular pathways. If BC is not diagnosed early, complications may lead to death. Thus, the pursuit of novel therapeutic avenues persists, notably focusing on epigenetic pathways such as histone deacetylases (HDACs). The compound <i>N</i>-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA), a derivative of valproic acid (VPA), has emerged as a promising candidate warranting pre-clinical investigation. HO-AAVPA is an HDAC inhibitor with antiproliferative effects on BC, but its molecular mechanism has yet to be deciphered. Furthermore, in the present study, we determined the metabolomic effects of HO-AAVPA and VPA on cells of luminal breast cancer (MCF-7) and triple-negative breast cancer (MDA-MB-231) subtypes. The LC-MS untargeted metabolomic study allowed for the simultaneous measurement of multiple metabolites and pathways, identifying that both compounds affect glycerophospholipid and sphingolipid metabolism in the MCF-7 and MDA-MB-231 cell lines, suggesting that other biological targets were different from HDACs. In addition, there are different dysregulate metabolites, possibly due to the physicochemical differences between HO-AAVPA and VPA.https://www.mdpi.com/1422-0067/24/19/14543metabolomicsbreast cancervalproic acidHO-AAVPAMDA-MB-231MCF-7 |
| spellingShingle | Alan Rubén Estrada-Pérez Juan Benjamín García-Vázquez Humberto L. Mendoza-Figueroa Martha Cecilia Rosales-Hernández Cynthia Fernández-Pomares José Correa-Basurto Untargeted LC-MS/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell Lines International Journal of Molecular Sciences metabolomics breast cancer valproic acid HO-AAVPA MDA-MB-231 MCF-7 |
| title | Untargeted LC-MS/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell Lines |
| title_full | Untargeted LC-MS/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell Lines |
| title_fullStr | Untargeted LC-MS/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell Lines |
| title_full_unstemmed | Untargeted LC-MS/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell Lines |
| title_short | Untargeted LC-MS/MS Metabolomics Study of HO-AAVPA and VPA on Breast Cancer Cell Lines |
| title_sort | untargeted lc ms ms metabolomics study of ho aavpa and vpa on breast cancer cell lines |
| topic | metabolomics breast cancer valproic acid HO-AAVPA MDA-MB-231 MCF-7 |
| url | https://www.mdpi.com/1422-0067/24/19/14543 |
| work_keys_str_mv | AT alanrubenestradaperez untargetedlcmsmsmetabolomicsstudyofhoaavpaandvpaonbreastcancercelllines AT juanbenjamingarciavazquez untargetedlcmsmsmetabolomicsstudyofhoaavpaandvpaonbreastcancercelllines AT humbertolmendozafigueroa untargetedlcmsmsmetabolomicsstudyofhoaavpaandvpaonbreastcancercelllines AT marthaceciliarosaleshernandez untargetedlcmsmsmetabolomicsstudyofhoaavpaandvpaonbreastcancercelllines AT cynthiafernandezpomares untargetedlcmsmsmetabolomicsstudyofhoaavpaandvpaonbreastcancercelllines AT josecorreabasurto untargetedlcmsmsmetabolomicsstudyofhoaavpaandvpaonbreastcancercelllines |