A Dicitore1, E S Grassi2, M O Borghi2,3, G Gelmini1, M C Cantone2, G Gaudenzi2, L Persani1,2, M Caraglia4, G Vitale5,6. 1. Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, via Zucchi 18, Cusano Milanino (Mi), 20095, Milan, Italy. 2. Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy. 3. Experimental Laboratory of Immuno-rheumatology, Istituto Auxologico Italiano IRCCS, Milan, Italy. 4. Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy. 5. Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, via Zucchi 18, Cusano Milanino (Mi), 20095, Milan, Italy. giovanni.vitale@unimi.it. 6. Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy. giovanni.vitale@unimi.it.
Abstract
PURPOSE: 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.
PURPOSE: 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.
Entities:
Keywords:
Apoptosis; Castration-resistant prostate cancer; Cell cycle; Interferon beta; Type I interferons
Authors: Peter M van Koetsveld; Giovanni Vitale; Wouter W de Herder; Richard A Feelders; Katy van der Wansem; Marlijn Waaijers; Casper H J van Eijck; Ernst-Jan M Speel; Ed Croze; Aart-Jan van der Lely; Steven W J Lamberts; Leo J Hofland Journal: J Clin Endocrinol Metab Date: 2006-08-15 Impact factor: 5.958
Authors: Miranda M C van Beers; Melody Sauerborn; Francesca Gilli; Vera Brinks; Huub Schellekens; Wim Jiskoot Journal: Pharm Res Date: 2011-05-05 Impact factor: 4.200
Authors: Giovanni Vitale; Peter M van Koetsveld; Wouter W de Herder; Katy van der Wansem; Joop A M J L Janssen; Annamaria Colao; Gaetano Lombardi; Steven W J Lamberts; Leo J Hofland Journal: Am J Physiol Endocrinol Metab Date: 2009-01-13 Impact factor: 4.310
Authors: Viviana M Bimonte; Francesco Marampon; Ambra Antonioni; Simona Fittipaldi; Elisabetta Ferretti; Richard G Pestell; Mariaignazia Curreli; Andrea Lenzi; Giovanni Vitale; Antonio Brunetti; Silvia Migliaccio; Antonio Aversa Journal: Int J Mol Sci Date: 2021-01-13 Impact factor: 5.923
Authors: Kandarp M Dave; Linjiang Han; Meredith A Jackson; Lindsay Kadlecik; Craig L Duvall; Devika S Manickam Journal: Pharm Res Date: 2020-08-28 Impact factor: 4.580