title: Key extracellular and intracellular steps in the antitumor action of seminal ribonuclease.
abstract: Bovine seminal ribonuclease (RNase) is a cytotoxin with a selective action toward tumor cells. We report here the results of an investigation that elucidate key extracellular and intracellular steps of the mechanism of its antitumor action. Seminal RNase is found to bind specifically to a large number of binding sites on the extracellular matrix of target cells, whereas other homologous RNases, including a monomeric derivative of the protein, do not bind. The key role of the pericellular matrix is confirmed by the finding that malignant cells grown in suspension bind negligible amounts of protein, and are resistant to its toxic effects, whereas the same cells, grown in monolayers, bind high amounts of seminal RNase and are killed by the protein. Seminal RNase is internalized by malignant cells, where it degrades rRNA and inhibits protein synthesis. These effects are not detectable when catalytically inactivated enzyme, or a catalytically active, monomeric derivative of the enzymes, are employed. The enzyme is bound and internalized also by the corresponding non-malignant cells, but no effects are detectable on RNA stability and on protein synthesis in these cells. This might be attributed to a different intracellular management in normal cells of the cytotoxic protein.
authors.affiliation: Department of Organic and Biological Chemistry, University of Naples, Federico II, Italy.
authors.forename: M R
authors.initials: MR
authors.lastname: Mastronicola
authors.forename: R
authors.initials: R
authors.lastname: Piccoli
authors.forename: G
authors.initials: G
authors.lastname: D'Alessio
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001665:Binding Sites; D016466:CHO Cells; D002461:Cell Line, Transformed; D006224:Cricetinae; D004722:Endoribonucleases / Q000378:metabolism / Q000494:pharmacology*; D005109:Extracellular Matrix / Q000378:metabolism; D051379:Mice
chemical_list: D000970:Antineoplastic Agents; D004722:Endoribonucleases; C032523:ribonuclease SPL