Inhibition of radiation-induced transformation of C3H/10T1/2 cells by specific protease substrates

Abstract

In the current studies, we have examined the effect of two specific protease substrates, the thrombin substrate Boc-Val-Pro-Arg-MCA and the chymotrypsin substrate Suc-Ala-Ala-Pro-Phe-MCA, on the oncogenic transformation of C3H/10T1/2 cells induced with: (i) 6 Gy of X-radiation and (ii) 4 Gy of X-radiation followed by promotion with 12-O-tetradecanoylphorbol-13-acetate (TPA). Both substrates reduced radiation transformation while only Suc-Ala-Ala-Pro-Phe-MCA suppressed the TPA enhancement of radiation transformation. We have previously reported that C3H/10T1/2 cells contain at least two proteolytic activities which will cleave these substrates. Our results therefore suggest that: (i) these substrates may inhibit oncogenic transformation due to the fact that they are competitive substrates for these enzymes; and (ii) two or more proteases play an important role in the malignant transformation of these cells.

Field bean protease inhibitor preparations, unlike methotrexate, can completely suppress Yoshida sarcoma tumor in rats

“…Since the carcinogenesis process involves the participation of proteases and the anticarcinogenic action of protease inhibitors is attributed to their blocking action on these proteases Billings et al, 1990a ;Kennedy, 1993b), we examined the possibility of the oncosuppressive activity of the field bean protease inhibitor being related to its ability to inhibit the sarcoma cell proteases. For this, homogenates of sarcoma cells, isolated freshly from ascitic fluid were assessed for protease activity on gelatin containing zymograms.…”

Protease Inhibitors in Chemoprevention of Cancer: An overview

“…In that case, the role of protease inhibitors in chemoprevention would be an indirect one. Billings et al (77)(78)(79) hypothesized that protease inhibitors inhibit cellular enzymes which induce or regulate transformation. It has been demonstrated that a potatoderived chymotrypsin inhibitor and soyabean derived Bowman-Birk inhibitor blocked the enzymatic cleavage of a peptide substrate (80) and thus suppressed malignant transformation.…”