FIELD BEAN PROTEASE INHIBITOR PREPARATION, UNLIKE METHOTREXATE, CAN COMPLETELY SUPPRESS YOSHIDA SARCOMA TUMOR IN RATS

Protease inhibitor preparations (PIP) with antitryptic and antichymotr yptic activities isolated from field bean legume as well as doxorubici n and cyclophosphamide could effectively suppress the growth of Yoshid a sarcoma ascites tumor cells transplanted in adult rats and prevent t heir death. As against this, methotrexate and heat-inactivated PIP wer e ineffective in such rats at varied doses of treatment tried. The per cent survival of animals appeared to be related to the purity, treatme nt mode and the dose of PIP used. Zymographic analysis of the trypsin activated sarcoma cell homogenate revealed the presence of six proteas e bands in the molecular weight range of 51kD to 206kD. Prolonged inte ractions of such zymograms with protease inhibitors such as 20mM EDTA or 5mM diisopropyl fluorophosphate (DIFP) or 400.mu g/ml of PIP in rea ction buffer indicated that these are not metalloproteases but serine proteases whose activities are inhibited by PIP and DIFP. Since protea ses are involved in cell growth regulation and cell transformation, we hypothesize a positive relationship between the field bean protease i nhibitor's blocking action on tumor cell proteases and its tumor suppr essing activity