title: TCTP is a critical survival factor that protects cancer cells from oxidative stress-induced cell-death.
abstract: The translationally controlled tumor protein (TCTP) displays growth-promoting and antiapoptotic properties. To gain information on the role of TCTP in cancer disease, we studied the modulation of TCTP and cell survival under stress conditions on tumor cell lines of different origins. When cancer cells were exposed to a mild oxidative stress, such low doses of Arsenic trioxide (ATO) or hydrogen peroxide (H(2)O(2)), up-regulation of TCTP was observed in cells survived to the treatment. Differently, a strong oxidative hit provided by ATO combined with glutathione (GSH) depletion or condition of glucose deprivation caused a down-modulation of TCTP followed by cell death. Clones with a forced expression of TCTP or with silenced TCTP were obtained from the breast cancer cell line MDA-MB-231. The sensitivity to oxidative stress was strongly enhanced in down-modulated TCTP cells while decreasing in cells with high levels of TCTP. Together these results indicate that TCTP is a survival factor that protects cancer cells from oxidative stress-induced cell-death. We propose TCTP as a "stress hallmark" that may be exploited as a therapeutic target to decrease the resistance of cancer cells to anticancer therapy.
authors.affiliation: Institute of Translational Pharmacology, National Research Council, Rome, Italy. maria.lucibello@ift.cnr.it
authors.forename: Maria
authors.initials: M
authors.lastname: Lucibello
authors.forename: Alessandra
authors.initials: A
authors.lastname: Gambacurta
authors.forename: Manuela
authors.initials: M
authors.lastname: Zonfrillo
authors.forename: Pasquale
authors.initials: P
authors.lastname: Pierimarchi
authors.forename: Annalucia
authors.initials: A
authors.lastname: Serafino
authors.forename: Guido
authors.initials: G
authors.lastname: Rasi
authors.forename: Anna
authors.initials: A
authors.lastname: Rubartelli
authors.forename: Enrico
authors.initials: E
authors.lastname: Garaci
mesh_terms: D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000494:pharmacology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress; D010087:Oxides / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D000090324:Tumor Protein, Translationally-Controlled 1
chemical_list: D001152:Arsenicals; D014408:Biomarkers, Tumor; D010087:Oxides; C000715647:TPT1 protein, human; D000090324:Tumor Protein, Translationally-Controlled 1; D006861:Hydrogen Peroxide; D005978:Glutathione; D000077237:Arsenic Trioxide