A Proteomics Approach Identifies RREB1 as a Crucial Molecular Target of Imidazo–Pyrazole Treatment in SKMEL-28 Melanoma Cells

Author:

Iervasi Erika1ORCID,Coronel Vargas Gabriela1ORCID,Bachetti Tiziana1,Tkachenko Kateryna1,Spallarossa Andrea2ORCID,Brullo Chiara2ORCID,Rosano Camillo1ORCID,Carta Sonia3ORCID,Barboro Paola1ORCID,Profumo Aldo1ORCID,Ponassi Marco1ORCID

Affiliation:

1. IRCCS Ospedale Policlinico San Martino, Proteomics and Mass Spectrometry Unit, L.go. R. Benzi, 10, 16132 Genova, Italy

2. Department of Pharmacy, Section of Medicinal Chemistry, University of Genoa, Viale Benedetto XV 3, 16132 Genova, Italy

3. IRCCS Ospedale Policlinico San Martino, Nuclear Medicine Unit, L.go. R. Benzi, 10, 16132 Genova, Italy

Abstract

Cutaneous melanoma is the most dangerous and deadly form of human skin malignancy. Despite its rarity, it accounts for a staggering 80% of deaths attributed to cutaneous cancers overall. Moreover, its final stages often exhibit resistance to drug treatments, resulting in unfavorable outcomes. Hence, ensuring access to novel and improved chemotherapeutic agents is imperative for patients grappling with this severe ailment. Pyrazole and its fused systems derived thereof are heteroaromatic moieties widely employed in medicinal chemistry to develop effective drugs for various therapeutic areas, including inflammation, pain, oxidation, pathogens, depression, and fever. In a previous study, we described the biochemical properties of a newly synthesized group of imidazo–pyrazole compounds. In this paper, to improve our knowledge of the pharmacological properties of these molecules, we conduct a differential proteomic analysis on a human melanoma cell line treated with one of these imidazo–pyrazole derivatives. Our results detail the changes to the SKMEL-28 cell line proteome induced by 24, 48, and 72 h of 3e imidazo–pyrazole treatment. Notably, we highlight the down-regulation of the Ras-responsive element binding protein 1 (RREB1), a member of the zinc finger transcription factors family involved in the tumorigenesis of melanoma. RREB1 is a downstream element of the MAPK pathway, and its activation is mediated by ERK1/2 through phosphorylation.

Funder

Italian Ministry of Health

“Più unici che rari” OdV

Publisher

MDPI AG

同舟云学术

1.学者识别学者识别

2.学术分析学术分析

3.人才评估人才评估

"同舟云学术"是以全球学者为主线,采集、加工和组织学术论文而形成的新型学术文献查询和分析系统,可以对全球学者进行文献检索和人才价值评估。用户可以通过关注某些学科领域的顶尖人物而持续追踪该领域的学科进展和研究前沿。经过近期的数据扩容,当前同舟云学术共收录了国内外主流学术期刊6万余种,收集的期刊论文及会议论文总量共计约1.5亿篇,并以每天添加12000余篇中外论文的速度递增。我们也可以为用户提供个性化、定制化的学者数据。欢迎来电咨询!咨询电话:010-8811{复制后删除}0370

www.globalauthorid.com

TOP

Copyright © 2019-2024 北京同舟云网络信息技术有限公司
京公网安备11010802033243号  京ICP备18003416号-3