Antineoplastic ribonucleases selectively kill thyroid carcinoma cells via caspase-mediated induction of apoptosis.
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| Abstract |
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.
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| Authors | Daniela Spalletti-Cernia, Rosanna Sorrentino, Sonia Di Gaetano, Angela Arciello, Corrado Garbi, Renata Piccoli, Giuseppe D'Alessio, Giancarlo Vecchio, Paolo Laccetti, Massimo Santoro |
| Journal | The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 88 Issue 6 Pg. 2900-7 (Jun 2003) ISSN: 0021-972X [Print] United States |
| PMID | 12788904 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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