title: In vitro biological activity of bovine milk ribonuclease-4.
abstract: Several members of the ribonuclease superfamily possess a variety of interesting biological properties, including ribonucleolytic, angiogenic, antiproliferative, cytotoxic, embryotoxic, aspermatogenic and antitumoral activity. In this study, we report the purification from bovine milk of a protein with structural and enzymatic properties very similar to those of ribonuclease-4 (RNase-4), which is normally present in the liver and lungs, and examined its functional properties, biological activity and cytotoxic effects. RNase-4, at physiological concentrations, had a positive effect on the vitality and proliferation of human umbilical vein endothelial cells. Moreover, it induced an increase in cellular migration and the formation of in vitro capillary-like structures. We also evaluated the effect of RNase-4 in vitro on human breast, colorectal and cervical carcinoma cell lines. The protein was revealed to have a cytotoxic effect similar to that of RNase-A. We suggest that the positive effects of RNase-4 on normal cells were due to its particularly close interaction with RNase inhibitor, while good conformational stability and resistance to proteolytic degradation potentially favour ribonuclease cytotoxicity.
authors.affiliation: Department of Pharmaceutical Sciences, University of Padova, I-35128 Padova, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Di Liddo
authors.forename: D
authors.initials: D
authors.lastname: Dalzoppo
authors.forename: S
authors.initials: S
authors.lastname: Baiguera
authors.forename: M T
authors.initials: MT
authors.lastname: Conconi
authors.forename: M
authors.initials: M
authors.lastname: Dettin
authors.forename: P P
authors.initials: PP
authors.lastname: Parnigotto
authors.forename: C
authors.initials: C
authors.lastname: Grandi