title: rpL3 promotes the apoptosis of p53 mutated lung cancer cells by down-regulating CBS and NFκB upon 5-FU treatment.
abstract: 5-FU is a chemotherapy drug commonly used for the treatment of human cancers; however drug resistance represents a major challenge for its clinical application. In the present study, we reporte that rpL3 induced by 5-FU treatment in Calu-6 cells represses CBS transcription and reduces CBS protein stability leading to a decrease of CBS protein levels. rpL3 also regulates negatively the activation of NFκB by preventing NFκB nuclear translocation through IκB-α up-regulation. Furthermore, we demonstrate that rpL3 significantly enhances the apoptosis of 5-FU treated Calu-6 cells promoting the overexpression of the pro-apoptotic proteins Bax and the inhibition of the anti-apoptotic protein Bcl-2. We finally demonstrate that rpL3 potentiates 5-FU efficacy inhibiting cell migration and invasion. Our results suggest that combination of rpL3 and 5-FU is a promising strategy for chemotherapy of lung cancers lacking functional p53 that are resistant to 5-FU.
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131 Naples, Italy.
authors.forename: Annapina
authors.initials: A
authors.lastname: Russo
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131 Naples, Italy.
authors.forename: Assunta
authors.initials: A
authors.lastname: Saide
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131 Naples, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Cagliani
authors.affiliation: Department of Pathology, Istituto Nazionale Tumori "Fondazione Pascale"-IRCCS via Mariano Semmola, Napoli 80131, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Cantile
authors.affiliation: Department of Pathology, Istituto Nazionale Tumori "Fondazione Pascale"-IRCCS via Mariano Semmola, Napoli 80131, Italy.
authors.forename: Gerardo
authors.initials: G
authors.lastname: Botti
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via Domenico Montesano 49, 80131 Naples, Italy.
authors.forename: Giulia
authors.initials: G
authors.lastname: Russo
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003541:Cystathionine beta-Synthase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009154:Mutation; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000819:agonists / Q000235:genetics / Q000378:metabolism
chemical_list: D000964:Antimetabolites, Antineoplastic; C494826:BAX protein, human; C000595707:BCL2 protein, human; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; C000716547:RPL3 protein, human; D000090822:Ribosomal Protein L3; D012269:Ribosomal Proteins; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D000072000:NF-KappaB Inhibitor alpha; D003541:Cystathionine beta-Synthase; D005472:Fluorouracil