Antagonistic effect of a salivary proline-rich peptide on the cytosolic Ca2+ mobilization induced by progesterone in oral squamous cancer cells

Palmerini, Carlo Alberto;Mazzoni, Michela;Radicioni, Giorgia;Marzano, Valeria;Granieri, Letizia;Iavarone, Federica;Longhi, Renato;MESSANA, IRENE;CABRAS, TIZIANA;SANNA, MARIA TERESA;Castagnola, Massimo;Vitali, Alberto

2016-01-01

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Abstract

A salivary proline-rich peptide of 1932 Da showed a dose-dependent antagonistic effect on the cytosolic Ca2+ mobilization induced by progesterone in a tongue squamous carcinoma cell line. Structure-activity studies showed that the activity of the peptide resides in the Cterminal region characterized by a proline stretch flanked by basic residues. Furthermore, lack of activity of the retro-inverso peptide analogue suggested the involvement of stereospecific recognition. Mass spectrometry-based shotgun analysis, combined with Western blotting tests and biochemical data obtained with the Progesterone Receptor Membrane Component 1 (PGRMC1) inhibitor AG205, showed strong evidence that p1932 performs its modulatory action through an interaction with the progesterone receptor PGRMC1, which is predominantly expressed in this cell line and, clearly, plays a role in progesterone induced Ca2+ response. Thus, our results point to p1932 as a modulator of the transduction signal pathway mediated by this protein and, given a well-established involvement of PGRMC1 in tumorigenesis, highlight a possible therapeutic potential of p1932 for the treatment of oral cancer.