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.
Highlights
Cervical cancer (CC) is one of the most frequently diagnosed cancers in women worldwide, and it has a high mortality rate according to the World Health Organization [1,2], being the fourth leading cause of cancer death in females (7.5%) [3]
Some studies have explored histone deacetylases inhibitors (HDACi) for the treatment of cancers due to its cytotoxic effects inducing cell cycle arrest and apoptosis, among other anticancer effects [5,6]. This facts is due to HDACi acts inhibiting the activity of histone deacetylases (HDACs) enzymes which are responsible for deacetylating the ε-amino group on lysine on the tail of proteins, thereby regulating DNA transcription [6]
C8 indicates that the ligand did nTohterreeafocrhe,thweeptreostteeidn thcaetainlyvtiictrositienhainbditotrhyatacittivwitays oinf sHerOte-dAAinVPaAn iangvaeirntsetdHmDaAnCne1r, HinDtoAtCh8e, caantdalHytDicAtuCn6n.eOl.ur results indicated that HO-AAVPA inhibits HDAC1 (IC50 = 153.78 μM), while no inhibTithioernefworaes,owbesetrevseteddfothr eHiDnAvCitr6oainndhiHbiDtoAryC8a.ctTivhietryefoofreH, Oth-eAsAe VrePsAultasgcaoinrrsetlaHteDdAwCi1th, HdDocAkCin8g, arensdulHtsDsAhoCw6.inOgutrhraetsHulOts-AinAdVicPaAtedis tchaaptaHblOe -tAo AbeVaPcAcoimnhmiboidtsatHeDatAcCat1a(lyICti5c0 s=it1e5o3f.7H8DμAMC),1wenhzilyemneo, inhibition was observed for HDAC6 and HDAC8
Summary
Cervical cancer (CC) is one of the most frequently diagnosed cancers in women worldwide, and it has a high mortality rate according to the World Health Organization [1,2], being the fourth leading cause of cancer death in females (7.5%) [3]. It has been estimated that approximately 5 million people will die from HPV-infection-induced CC over the two decades, making it necessary to treat CC to decrease mortality [4]. In this sense, some studies have explored histone deacetylases inhibitors (HDACi) for the treatment of cancers due to its cytotoxic effects inducing cell cycle arrest and apoptosis, among other anticancer effects [5,6]. HDAC class III (sirtuins 1-7) utilizes NAD+ as a cofactor [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
