title: Antitumor activity of interferon-β1a in hormone refractory prostate cancer with neuroendocrine differentiation.
abstract: OBJECTIVE
  Type I interferons (IFN-α and IFN-β) are a class of cytokines that exert several biological activities, such as modulation of cell proliferation and differentiation and of the immune system. Although these cytokines interact with a common receptor complex, IFN-β showed a more potent antitumor activity than IFN-α in several tumor models. New recombinant human IFN-β products, such as IFN-β1a and IFN-β1b, have been produced in order to improve the stability and bioavailability of natural IFN-β. In this report, we analyzed the effects of recombinant IFN-β1a on the cell proliferation of two human androgen-resistant prostate cancer cell lines with neuroendocrine differentiation (DU-145, PC-3) and related mechanisms of action.
  
  
  METHODS
  The effects of IFN-β1a on the cell growth proliferation, cell cycle, and apoptosis have been evaluated in DU-145 and PC-3 cells through MTT assay, DNA flow cytometry with propidium iodide, and Annexin V-FITC/propidium iodide staining, respectively. Moreover, the expression of neuron-specific enolase (NSE), cleaved caspase-3, caspase-8, and PARP was evaluated through Western blotting.
  
  
  RESULTS
  IFN-β1a showed a significant anti-proliferative activity in both androgen-resistant cell lines. This effect was related to cell cycle perturbation and induction in apoptosis, as shown by flow cytometric analysis, the activation of caspase-3 and caspase-8 and PARP cleavage during incubation with IFN-β1a. Moreover, this cytokine reduced the expression of NSE in both cell lines.
  
  
  CONCLUSIONS
  Recombinant IFN-β1a (Rebif) showed a potent in vitro anti-proliferative activity in androgen-resistant prostate cancer cells, and it could represent a promising tool for the treatment of this tumor.
authors.affiliation: Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, via Zucchi 18, Cusano Milanino (Mi), 20095, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Dicitore
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.
authors.forename: E S
authors.initials: ES
authors.lastname: Grassi
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.|Experimental Laboratory of Immuno-rheumatology, Istituto Auxologico Italiano IRCCS, Milan, Italy.
authors.forename: M O
authors.initials: MO
authors.lastname: Borghi
authors.affiliation: Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, via Zucchi 18, Cusano Milanino (Mi), 20095, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gelmini
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Cantone
authors.affiliation: Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Gaudenzi
authors.affiliation: Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, via Zucchi 18, Cusano Milanino (Mi), 20095, Milan, Italy.|Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Persani
authors.affiliation: Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Caraglia
authors.affiliation: Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, via Zucchi 18, Cusano Milanino (Mi), 20095, Milan, Italy. giovanni.vitale@unimi.it.|Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy. giovanni.vitale@unimi.it.
authors.forename: G
authors.identifier: http://orcid.org/0000-0003-2478-683X
authors.initials: G
authors.lastname: Vitale
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D000068556:Interferon beta-1a / Q000494:pharmacology*; D008297:Male; D018358:Neuroendocrine Tumors / Q000188:drug therapy* / Q000473:pathology; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000473:pathology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000068556:Interferon beta-1a
keywords: Apoptosis; Castration-resistant prostate cancer; Cell cycle; Interferon beta; Type I interferons