Keywords: Benzyloxycarbonylvalylalanylaspartyl Fluoromethylketone, Bovine Seminal Ribonuclease, Caspase, Caspase Inhibitor, Nicotinamide Adenine Dinucleotide Adenosine Diphosphate Ribosyltransferase, Pancreatic Ribonuclease, Protein Kinase B, Protein Serine Threonine Kinase, Unclassified Drug, Animal Experiment, Animal Model, Antineoplastic Activity, Apoptosis, Article, Cancer Cell, Cancer Cell Culture, Carcinoma Cell, Cell Killing, Cell Survival, Controlled Study, Drug Effect, Drug Selectivity, Human, Human Cell, Mouse, Nonhuman, Nude Mouse, Priority Journal, Protein Degradation, Protein Phosphorylation, Thyroid Carcinoma, Amino Acid Chloromethyl Ketones, Antineoplastic Agents, Cysteine Proteinase Inhibitors, Endoribonucleases, Protein-Serine-Threonine Kinases, Proto-Oncogene Proteins, Proto-Oncogene Proteins C-Akt, Thyroid Neoplasms, Tumor Cells, Mus Musculus,
Affiliations: *** IBB - CNR ***
Ist. Endocrinol. Oncol. Sperim. C., Dipto. Biol. e Patol. Cell. e Molec., Univ. di Napoli Federico II, 80131 Naples, Italy
Dipartimento di Chimica Biologica, Univ. di Napoli Federico II, 80134 Naples, Italy
Ist. Biostrutture e Bioimmagini-CNR, 80134 Naples, Italy
References: Not available.
Antineoplastic ribonucleases selectively kill thyroid carcinoma cells via caspase-mediated induction of apoptosis
Bovine seminal ribonuclease ( BS- RNase), a natural dimeric homolog of bovine pancreatic RNase ( RNase A), and HHP2-RNase, an engineered dimeric form of human pancreatic RNase ( HP- RNase), are endowed with powerful antitumor effects. Here we show that BS- and HHP2- RNases, but not monomeric RNase A, induce apoptosis of human thyroid carcinoma cell lines. RNase- induced apoptosis was associated with activation of initiation caspase- 8 and - 9. This was followed by activation of executioner caspase- 3, leading to the proteolytic cleavage of poly( ADP- ribose) polymerase. The caspase inhibitor Z- Val- Ala- Asp-( OMe)- fluoromethylketone protected thyroid cancer cells from BS- RNase- induced apoptosis. RNase- triggered apoptosis and caspase activation were accompanied by reduced phosphorylation of Akt/ protein kinase B ( PKB), a serine- threonine kinase that when phosphorylated is able to deliver survival signals to cancer cells. BS- RNase antitumor effects in nude mice were accompanied by caspase activation and apoptosis. Because of the high selectivity of apoptotic effects for malignant cells, BS- and HHP2- RNase are promising tools for the treatment of aggressive thyroid cancer.
Antineoplastic ribonucleases selectively kill thyroid carcinoma cells via caspase-mediated induction of apoptosis
No results.
Antineoplastic ribonucleases selectively kill thyroid carcinoma cells via caspase-mediated induction of apoptosis