Enhanced cytotoxic activity of a bifunctional chimeric protein containing a type 1 ribosome-inactivating protein and a serine protease inhibitor.
Both ribosome-inactivating proteins (RIPs) and plant proteinase inhibitors, belong to protein families known to regulate cellular homeostasis and likely involved in plant defense. Nevertheless the interest in these protein classes is due to their potential use for the treatment of several important human diseases such as cancer. Thus, in the present study, type 1 ribosome-inactivating protein and wheat subtilisin/chymotrypsin inhibitor, were engineered into a chimeric protein with cytotoxic action selective for murine tumor cells, while lacking any appreciable toxicity on murine normal cells. This chimeric protein selectively sensitizes to apoptotic death cells derived from Simian-virus-40-transformed mouse fibroblasts (SVT2 cells). The cytotoxicity of this new recombinant product has been detected also on three different human malignant cells. Therefore action on tumor cells of this protein could represent a potentially very attractive novel tool for anticancer drug design.
Dipartimento di Scienze della Vita, Seconda Università di Napoli, Via Vivaldi 43, I-81100 Caserta, Italy.
Rachele
R
Tamburino
Elio
E
Pizzo
Carmen
C
Sarcinelli
Elia
E
Poerio
Francesca
F
Tedeschi
Anna G
AG
Ficca
Augusto
A
Parente
Antimo
A
Di Maro
D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003001:Cloning, Molecular; D006801:Humans; D051379:Mice; D029603:Phytolacca / Q000235:genetics; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D054789:Ribosome Inactivating Proteins, Type 1 / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010940:Plant Proteins; D011993:Recombinant Fusion Proteins; D054789:Ribosome Inactivating Proteins, Type 1; D015842:Serine Proteinase Inhibitors; C504099:WSCI protein, Triticum