tailieunhanh - Báo cáo khóa học: Noncytotoxic ribonuclease, RNase T1, induces tumor cell death via hemagglutinating virus of Japan envelope vector

Several ribonucleases, including onconase anda-sarcin, are known to be toxic to tumor cells. On the other hand, although its structure is relatedto thatofa-sarcin,RNase T1 is noncytotoxic because of its inability to internalize into tumor cells. In this study, we internalized RNase T1 into human tumor cells via a novel gene transfer reagent, hem-agglutinating virus of Japan (HVJ) envelope vector, which resulted in cell death. This cytotoxicity was drastically increased by pretreatment of HVJ envelope vector with protamine sulfate, and was stronger than that of onconase, which is inphase III human clinical trials as a nonmutagenic cancer chemotherapeutic agent. . | Eur. J. Biochem. 271 3567-3572 2004 FEBS 2004 doi Noncytotoxic ribonuclease RNase T1 induces tumor cell death via hemagglutinating virus of Japan envelope vector Shunji Yuki Yoshitaka Kondo Fuminori Kato Masanari Kato and Norifusa Matsuo Central Research Institute Ishihara Sangyo Kaisha Ltd Kusatsu Shiga Japan Several ribonucleases including onconase and a-sarcin are known to be toxic to tumor cells. On the other hand although its structure is related to that of a-sarcin RNase T1 is noncytotoxic because of its inability to internalize into tumor cells. In this study we internalized RNase T1 into human tumor cells via a novel gene transfer reagent hemagglutinating virus of Japan HVJ envelope vector which resulted in cell death. This cytotoxicity was drastically increased by pretreatment of HVJ envelope vector with protamine sulfate and was stronger than that of onconase which is in phase III human clinical trials as a nonmutagenic cancer chemotherapeutic agent. Furthermore internalized RNase T1 induced apoptotic cell death programs. Because its cytotoxicity is unfortunately not specific to tumor cells it cannot at present be developed as an anticancer drug. However we believe that RNase T1 incorporated in HVJ envelope vector will be a unique anticancer drug if HVJ envelope vector can be targeted to tumor cells. Keywords apoptosis HVJ envelope vector protein transfection RNase T1 tumor cell death. Ribonucleases are best known for their ability to cleave RNA. However some of these proteins have been shown to be much more than digestive enzymes. For example two groups of these enzymes have antitumor activities 1-4 . One is the family of fungal ribotoxins that specifically cleave one phosphodiester bond of the larger rRNA at a highly conserved region inhibit protein synthesis and eventually cause cell death 3 4 while the other is composed of certain members of the bovine pancreatic RNase A superfamily. Onconase a homolog of RNase A from