N-(2′-hydroxyphenyl)-2-propylpentanamide (ho-aavpa) inhibits hdac1 and increases the translocation of hmgb1 levels in human cervical cancer cells

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

doi:10.3390/ijms21165873

N-(2^′-hydroxyphenyl)-2-propylpentanamide (ho-aavpa) inhibits hdac1 and increases the translocation of hmgb1 levels in human cervical cancer cells

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

Escuela Superior de Medicina (ESM)

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

N-(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.

Original language	English
Article number	5873
Pages (from-to)	1-14
Number of pages	14
Journal	International Journal of Molecular Sciences
Volume	21
Issue number	16
DOIs	https://doi.org/10.3390/ijms21165873
State	Published - 2 Aug 2020

Keywords

HDAC1 inhibition
HMGB1
HO-AAVPA compound
SiHa cells
Valproic acid

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms21165873

Cite this

Sixto-López, Y., Rosales-Hernández, M. C., de Oca, A. C. M., Fragoso-Morales, L. G., Mendieta-Wejebe, J. E., Correa-Basurto, A. M., Abarca-Rojano, E., & Correa-Basurto, J. (2020). N-(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, 21(16), 1-14. Article 5873. https://doi.org/10.3390/ijms21165873

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title = "N-(2′-hydroxyphenyl)-2-propylpentanamide (ho-aavpa) inhibits hdac1 and increases the translocation of hmgb1 levels in human cervical cancer cells",

abstract = "N-(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.",

keywords = "HDAC1 inhibition, HMGB1, HO-AAVPA compound, SiHa cells, Valproic acid",

author = "Yudibeth Sixto-L{\'o}pez and Rosales-Hern{\'a}ndez, {Martha Cecilia} and {de Oca}, {Arturo Contis Montes} and Fragoso-Morales, {Leticia Guadalupe} and Mendieta-Wejebe, {Jessica Elena} and Correa-Basurto, {Ana Mar{\'i}a} and Edgar Abarca-Rojano and Jos{\'e} Correa-Basurto",

note = "Publisher Copyright: {\textcopyright} 2020 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2020",

month = aug,

day = "2",

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Sixto-López, Y, Rosales-Hernández, MC, de Oca, ACM, Fragoso-Morales, LG, Mendieta-Wejebe, JE, Correa-Basurto, AM, Abarca-Rojano, E & Correa-Basurto, J 2020, 'N-(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, vol. 21, no. 16, 5873, pp. 1-14. https://doi.org/10.3390/ijms21165873

N-(2^′-hydroxyphenyl)-2-propylpentanamide (ho-aavpa) inhibits hdac1 and increases the translocation of hmgb1 levels in human cervical cancer cells. / Sixto-López, Yudibeth; Rosales-Hernández, Martha Cecilia; de Oca, Arturo Contis Montes et al.
In: International Journal of Molecular Sciences, Vol. 21, No. 16, 5873, 02.08.2020, p. 1-14.

Research output: Contribution to journal › Article › peer-review

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T1 - N-(2′-hydroxyphenyl)-2-propylpentanamide (ho-aavpa) inhibits hdac1 and increases the translocation of hmgb1 levels in human cervical cancer cells

AU - Sixto-López, Yudibeth

AU - Rosales-Hernández, Martha Cecilia

AU - de Oca, Arturo Contis Montes

AU - Fragoso-Morales, Leticia Guadalupe

AU - Mendieta-Wejebe, Jessica Elena

AU - Correa-Basurto, Ana María

AU - Abarca-Rojano, Edgar

AU - Correa-Basurto, José

PY - 2020/8/2

Y1 - 2020/8/2

N2 - N-(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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KW - SiHa cells

KW - Valproic acid

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