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.