<i>N</i>-(2′-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Inhibits HDAC1 and Increases the Translocation of HMGB1 Levels in Human Cervical Cancer Cells
<i>N</i>-(2′-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) is a VPA derivative designed to be a histone deacetylase (HDAC) inhibitor. HO-AAVPA has better antiproliferative effect than VPA in cancer cell lines. Therefore, in this work, the inhibitory effect of HO-AAVPA on HDAC1, HDAC6, an...
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2020-08-01
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author | Yudibeth Sixto-López Martha Cecilia Rosales-Hernández Arturo Contis-Montes de Oca Leticia Guadalupe Fragoso-Morales Jessica Elena Mendieta-Wejebe Ana María Correa-Basurto Edgar Abarca-Rojano José Correa-Basurto |
author_facet | Yudibeth Sixto-López Martha Cecilia Rosales-Hernández Arturo Contis-Montes de Oca Leticia Guadalupe Fragoso-Morales Jessica Elena Mendieta-Wejebe Ana María Correa-Basurto Edgar Abarca-Rojano José Correa-Basurto |
author_sort | Yudibeth Sixto-López |
collection | DOAJ |
description | <i>N</i>-(2′-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) is a VPA derivative designed to be a histone deacetylase (HDAC) inhibitor. HO-AAVPA has better antiproliferative effect than VPA in cancer cell lines. Therefore, in this work, the inhibitory effect of HO-AAVPA on HDAC1, HDAC6, and HDAC8 was determined by in silico and in vitro enzymatic assay. Furthermore, its antiproliferative effect on the cervical cancer cell line (SiHa) and the translocation of HMGB1 and ROS production were evaluated. The results showed that HO-AAVPA inhibits HDAC1, which could be related with HMGB1 translocation from the nucleus to the cytoplasm due to HDAC1 being involved in the deacetylation of HMGB1. Furthermore, an increase in ROS production was observed after the treatment with HO-AAVPA, which also could contribute to HMGB1 translocation. Therefore, the results suggest that one of the possible antiproliferative mechanisms of HO-AAVPA is by HDAC1 inhibition which entails HMGB1 translocation and ROS increased levels that could trigger the cell apoptosis. |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T17:22:37Z |
publishDate | 2020-08-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-9619fb8e097049968460e104a3a944622023-11-20T10:18:01ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-08-012116587310.3390/ijms21165873<i>N</i>-(2′-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Inhibits HDAC1 and Increases the Translocation of HMGB1 Levels in Human Cervical Cancer CellsYudibeth Sixto-López0Martha Cecilia Rosales-Hernández1Arturo Contis-Montes de Oca2Leticia Guadalupe Fragoso-Morales3Jessica Elena Mendieta-Wejebe4Ana María Correa-Basurto5Edgar Abarca-Rojano6José Correa-Basurto7Laboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica), Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador 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 Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, MexicoLaboratorio de Bioquímica, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador 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 Salvador 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 Salvador 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 Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, MexicoLaboratorio de Respiración Celular, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, MexicoLaboratorio de Diseño y Desarrollo de Nuevos Fármacos e Innovación Biotecnológica), Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomás, Ciudad de México 11340, Mexico<i>N</i>-(2′-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA) is a VPA derivative designed to be a histone deacetylase (HDAC) inhibitor. HO-AAVPA has better antiproliferative effect than VPA in cancer cell lines. Therefore, in this work, the inhibitory effect of HO-AAVPA on HDAC1, HDAC6, and HDAC8 was determined by in silico and in vitro enzymatic assay. Furthermore, its antiproliferative effect on the cervical cancer cell line (SiHa) and the translocation of HMGB1 and ROS production were evaluated. The results showed that HO-AAVPA inhibits HDAC1, which could be related with HMGB1 translocation from the nucleus to the cytoplasm due to HDAC1 being involved in the deacetylation of HMGB1. Furthermore, an increase in ROS production was observed after the treatment with HO-AAVPA, which also could contribute to HMGB1 translocation. Therefore, the results suggest that one of the possible antiproliferative mechanisms of HO-AAVPA is by HDAC1 inhibition which entails HMGB1 translocation and ROS increased levels that could trigger the cell apoptosis.https://www.mdpi.com/1422-0067/21/16/5873HO-AAVPA compoundHDAC1 inhibitionHMGB1SiHa cellsvalproic acid |
spellingShingle | Yudibeth Sixto-López Martha Cecilia Rosales-Hernández Arturo Contis-Montes de Oca Leticia Guadalupe Fragoso-Morales Jessica Elena Mendieta-Wejebe Ana María Correa-Basurto Edgar Abarca-Rojano José Correa-Basurto <i>N</i>-(2′-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Inhibits HDAC1 and Increases the Translocation of HMGB1 Levels in Human Cervical Cancer Cells International Journal of Molecular Sciences HO-AAVPA compound HDAC1 inhibition HMGB1 SiHa cells valproic acid |
title | <i>N</i>-(2′-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Inhibits HDAC1 and Increases the Translocation of HMGB1 Levels in Human Cervical Cancer Cells |
title_full | <i>N</i>-(2′-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Inhibits HDAC1 and Increases the Translocation of HMGB1 Levels in Human Cervical Cancer Cells |
title_fullStr | <i>N</i>-(2′-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Inhibits HDAC1 and Increases the Translocation of HMGB1 Levels in Human Cervical Cancer Cells |
title_full_unstemmed | <i>N</i>-(2′-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Inhibits HDAC1 and Increases the Translocation of HMGB1 Levels in Human Cervical Cancer Cells |
title_short | <i>N</i>-(2′-Hydroxyphenyl)-2-Propylpentanamide (HO-AAVPA) Inhibits HDAC1 and Increases the Translocation of HMGB1 Levels in Human Cervical Cancer Cells |
title_sort | i n i 2 hydroxyphenyl 2 propylpentanamide ho aavpa inhibits hdac1 and increases the translocation of hmgb1 levels in human cervical cancer cells |
topic | HO-AAVPA compound HDAC1 inhibition HMGB1 SiHa cells valproic acid |
url | https://www.mdpi.com/1422-0067/21/16/5873 |
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