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Antitumor activity of interferon-β1a in hormone refractory prostate cancer with neuroendocrine differentiation

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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.

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Acknowledgements

This work was supported by the Italian Ministry of Education, University and Research (FIRB RBAP11884 M) to GV and MC. The study was partially supported by funds of the Ricerca Corrente of Istituto Auxologico Italiano, Milan, Italy (code: 05C205_2012).

Funding

This study was funded by the Italian Ministry of Education, Research and University (grant number: FIRB RBAP11884 M). The study was partially supported by funds of the Ricerca Corrente of Istituto Auxologico Italiano, Milan, Italy (code: 05C205_2012) to GV.

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Authors and Affiliations

  1. Laboratory of Endocrine and Metabolic Research, Istituto Auxologico Italiano IRCCS, via Zucchi 18, Cusano Milanino (Mi), 20095, Milan, Italy

    A. Dicitore, G. Gelmini, L. Persani & G. Vitale

  2. Department of Clinical Sciences and Community Health (DISCCO), University of Milan, Milan, Italy

    E. S. Grassi, M. O. Borghi, M. C. Cantone, G. Gaudenzi, L. Persani & G. Vitale

  3. Experimental Laboratory of Immuno-rheumatology, Istituto Auxologico Italiano IRCCS, Milan, Italy

    M. O. Borghi

  4. Department of Biochemistry, Biophysics and General Pathology, Second University of Naples, Naples, Italy

    M. Caraglia

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  1. A. Dicitore
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  2. E. S. Grassi
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  3. M. O. Borghi
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  4. G. Gelmini
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  8. M. Caraglia
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  9. G. Vitale
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Correspondence to G. Vitale.

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Dicitore, A., Grassi, E.S., Borghi, M.O. et al. Antitumor activity of interferon-β1a in hormone refractory prostate cancer with neuroendocrine differentiation. J Endocrinol Invest 40, 761–770 (2017). https://doi.org/10.1007/s40618-017-0631-0

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