Noncytotoxic ribonuclease, RNase T1, induces tumor cell death via hemagglutinating virus of Japan envelope vector.
Several ribonucleases, including onconase and alpha-sarcin, are known to be toxic to tumor cells. On the other hand, although its structure is related to that of alpha-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.
Central Research Institute, Ishihara Sangyo Kaisha Ltd, Kusatsu, Shiga, Japan. s-yuki@iskweb.co.jp
Shunji
S
Yuki
Yoshitaka
Y
Kondo
Fuminori
F
Kato
Masanari
M
Kato
Norifusa
N
Matsuo
D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000378:metabolism*; D016923:Cell Death / Q000502:physiology*; D017326:Clinical Trials, Phase III as Topic; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D053938:DNA Fragmentation; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D011479:Protamines / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D006163:Ribonuclease T1 / Q000235:genetics / Q000378:metabolism*; D029082:Sendai virus / Q000235:genetics* / Q000378:metabolism*
D000590:Amino Acid Chloromethyl Ketones; D000970:Antineoplastic Agents; D015853:Cysteine Proteinase Inhibitors; D011479:Protamines; D011994:Recombinant Proteins; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D006163:Ribonuclease T1