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.
Antitumor activity of interferon-β1a in hormone refractory prostate cancer with neuroendocrine differentiation / A. Dicitore, E.S. Grassi, M.O. Borghi, G. Gelmini, M.C. Cantone, G. Gaudenzi, L. Persani, M. Caraglia, G. Vitale. - In: JOURNAL OF ENDOCRINOLOGICAL INVESTIGATION. - ISSN 0391-4097. - 40:7(2017 Jul), pp. 761-770.
|Titolo:||Antitumor activity of interferon-β1a in hormone refractory prostate cancer with neuroendocrine differentiation|
GRASSI, ELISA STELLARIA (Secondo)
VITALE, GIOVANNI (Ultimo)
|Parole Chiave:||apoptosis; castration-resistant prostate cancer; cell cycle; interferon beta; type I interferons; endocrinology, diabetes and metabolism; endocrinology|
|Settore Scientifico Disciplinare:||Settore MED/13 - Endocrinologia|
|Data di pubblicazione:||lug-2017|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/s40618-017-0631-0|
|Appare nelle tipologie:||01 - Articolo su periodico|