The antiproliferative and antitumor effect of wheat leaf
ribonuclease was tested in vitro on the human ML-2 cell line and in vivo on athymic nude mice bearing human
melanoma tumors. The antiproliferative activity of this plant
ribonuclease was negligible in comparison with
bovine seminal ribonuclease. In the experiments in vivo, a significant decrease of the
tumor size, however, was observed in the mice treated with wheat leaf
ribonuclease (27 kDa) compared with the control
RNase A and
polyethylene glycol. In nude mice injected intratumoraly with wheat leaf
ribonuclease, the
tumor size decreased from 100% in the control mice to 39% in treated mice. In the mice treated with
polyethylene glycol-conjugated wheat leaf
ribonuclease, the
tumor reduction was observed from 100 to 28%, whereas in counterparts treated with
polyethylene glycol-conjugated
bovine seminal ribonuclease the
tumor inhibition was reduced from 100 to 33%. Certain aspermatogenic and embryotoxic activity of wheat leaf
ribonuclease and
bovine seminal ribonuclease also appeared, but was lower in comparison with the effect of
onconase. Mutual immunological cross-reactivity between wheat leaf
ribonuclease antigens on one side and animal RNases (
bovine seminal ribonuclease,
RNase A, human HP-
RNase and
onconase) on the other side proved a certain structural similarity between animal and plant
ribonucleases. Immunogenicity of wheat leaf
ribonuclease was weaker in comparison with
bovine seminal ribonuclease (titer of
antibodies 160-320 against 1280-2560 in
bovine seminal ribonuclease). Interestingly, immunosuppressive effect of wheat leaf
ribonuclease tested on mixed lymphocyte culture-stimulated human lymphocytes reached the same level as that of bovine seminal
RNase. The
antibodies against wheat leaf
ribonuclease produced in the injected mice did not inactivate the
biological effect of this plant
RNase in vivo. This is probably the first paper in which plant
ribonuclease was used as antiproliferative and
antitumor drug against animal and human normal and
tumor cells and tissues in comparison with animal
ribonucleases.