A dimeric mutant of human pancreatic ribonuclease with selective cytotoxicity toward malignant cells.
Monomeric human pancreatic RNase, devoid of any biological activity other than its RNA degrading ability, was engineered into a dimeric protein with a cytotoxic action on mouse and human tumor cells, but lacking any appreciable toxicity on mouse and human normal cells. This dimeric variant of human pancreas RNase selectively sensitizes to apoptotic death cells derived from a human thyroid tumor. Because of its selectivity for tumor cells, and because of its human origin, this protein represents a potentially very attractive, novel tool for anticancer therapy.
Piccoli
R
R
Department of Organic and Biological Chemistry, University of Naples Federico II, Via Mezzocannone 16, 80134 Naples, Italy.
Di Gaetano
S
S
De Lorenzo
C
C
Grauso
M
M
Monaco
C
C
Spalletti-Cernia
D
D
Laccetti
P
P
Cinátl
J
J
Matousek
J
J
D'Alessio
G
G
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects*; D002471:Cell Transformation, Neoplastic; D019281:Dimerization; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000633:toxicity; D012259:Ribonuclease, Pancreatic / Q000737:chemistry / Q000235:genetics / Q000633:toxicity*; D012260:Ribonucleases / Q000737:chemistry; D012669:Seminal Vesicles / Q000201:enzymology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013964:Thyroid Neoplasms; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011994:Recombinant Proteins; D012260:Ribonucleases; D012259:Ribonuclease, Pancreatic