Antitumor activity of apoptotic nuclease TBN1 from L. esculentum.
Nuclease from tomato (TBN1) was produced by in planta biotechnology purified and tested for its anticarcinogenic properties. The nuclease was cytostatic after its intratumoral administration to nude mice bearing human melanoma or prostate carcinoma or after tumor targeting by TBN1 administration intravenously as conjugate with polyethylene glycol (PEG). Inhibitory effects of TBN1 on tumor growth were comparable to effects of bovine seminal RNase (BS-RNase), but the inhibition was reached at about ten times lower protein concentration. Simultaneously, TBN1 exhibited a lower degree of embryotoxicity compared to BS-RNAse and other nucleases. TBN1 showed significant stability in vivo, because it was readily detected after its administration intratumorally or intravenously by the fluorescence methods. Intravenous administration of TBN1-PEG caused significant inhibition of tumor proliferation without obvious degenerative changes, while direct administration of TBN1 into melanoma tumors led to rapid tumor tissue degeneration. The fact can be essential for the mode of TBN1 biological action that mature nuclease is a small (36 kDa) thermostable glycoprotein that has ability to destroy human 28S, 18S, 7S and 5.8S RNA, circular RNAs, double-stranded RNA in vitro and shows DNase and 3'nucleotidase activities.
Matousek
J
J
Biology Centre, Academy of Sciences of the Czech Republic v.v.i., Institute of Plant Molecular Biology, Czech Republic.
Podzimek
T
T
Pouckova
P
P
Stehlik
J
J
Skvor
J
J
Lipovova
P
P
Matousek
J
J
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002417:Cattle; D004622:Embryo, Mammalian / Q000201:enzymology / Q000473:pathology; D004706:Endodeoxyribonucleases / Q000494:pharmacology*; D005455:Fluorescent Antibody Technique; D006031:Glycosylation; D006801:Humans; D018551:Solanum lycopersicum / Q000201:enzymology; D008297:Male; D008546:Melanoma, Experimental / Q000473:pathology*; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000473:pathology*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D013736:Testicular Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D012330:RNA, Double-Stranded; D011994:Recombinant Proteins; D004706:Endodeoxyribonucleases