title: Proteomic analysis of cellular response to novel proapoptotic agents related to atypical retinoids in human IGROV-1 ovarian carcinoma cells.
abstract: Novel agents characterized by the scaffold of the atypical retinoid ST1926, but containing different chemical functions (carboxylic or hydroxamic acid), exhibit potent proapoptotic activity. In the present paper, we show that the treatment of the IGROV-1 ovarian cancer cell line with compounds sharing structural features with ST1926 (ST1898, ST3595, ST3056) determines a strong inhibition of proliferation mainly due to apoptotic cell death. In an effort to understand the mechanism of action of these compounds, we performed a proteomics analysis of IGROV-1 total lysates and nuclear extracts. Using this approach, we found that deregulation of calcium homeostasis, oxidative stress, cytoskeleton reorganization, and deregulation of proteasome function may represent important pathways involved in response of IGROV-1 cells to the studied compounds. The most prominent effect was down-regulation of factors involved in protein degradation, an event more marked in cells treated with ST3595. In addition, we identified proteins specifically modulated by each treatment, including prohibitin and cochaperone P23 (ST1898), pre-mRNA splicing factor SF2p32 and clathrin light chain (ST3595), as well as Far upstream element (FUSE) binding protein 1 and DNA-binding protein B (ST3056). By identifying proteins modulated by novel proapoptotic agents, this study provides insights into critical aspects of their mechanism of action.
authors.affiliation: Dipartimento di Biotecnologie, Laboratorio di Proteomica e Spettrometria di Massa, University of Verona, Strada le Grazie 15, 37134, Verona, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Milli
authors.forename: Paola
authors.initials: P
authors.lastname: Perego
authors.forename: Giovanni L
authors.initials: GL
authors.lastname: Beretta
authors.forename: Alice
authors.initials: A
authors.lastname: Corvo
authors.forename: Pier Giorgio
authors.initials: PG
authors.lastname: Righetti
authors.forename: Nives
authors.initials: N
authors.lastname: Carenini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Corna
authors.forename: Valentina
authors.initials: V
authors.lastname: Zuco
authors.forename: Franco
authors.initials: F
authors.lastname: Zunino
authors.forename: Daniela
authors.initials: D
authors.lastname: Cecconi
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D006801:Humans; D015394:Molecular Structure; D010051:Ovarian Neoplasms / Q000473:pathology*; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D012176:Retinoids / Q000737:chemistry* / Q000494:pharmacology*; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D020543:Proteome; D012176:Retinoids