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 C-terminal 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.
Highlights
Saliva is a mixed fluid, which is secreted by the major and minor salivary glands located in the oral cavity [1], and it exerts various protective and digestive functions [2]
Analytical and semipreparative Reversed Phase High Performance Liquid Chromatography (RP-HPLC) was carried out on a Tri Rotar-VI HPLC system equipped with a MD-910 multichannel detector for analytical purposes or with a Uvidec-100-VI variable UV detector for preparative purpose
Protein extracts were obtained by cell lysis with 50 mM Tris-HCl pH 8, 150 mM NaCl, 0.5% Deoxycholic acid, 0.1% SDS, 1% Nonidet P-40 (NP-40), 1 mM EDTA pH 8 supplemented with protease inhibitors (RIPA buffer)
Summary
Saliva is a mixed fluid, which is secreted by the major and minor salivary glands located in the oral cavity [1], and it exerts various protective and digestive functions [2]. We provide strong evidence that the modulatory role of p1932 is enabled via the PGRMC1 receptor, as shown by comparative protein expression studies and biochemical studies performed in the presence of AG-205, a specific inhibitor of PGRMC1 used alone and in combination with p1932. These results, highlight new prospects over the functional implications of salivary proline-rich peptides in cancer cell systems exposed to specific sexual hormones
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
