Inhibition of benzopyrene-induced forestomach tumors by field bean protease inhibitor(s).

Protease inhibitors (PIs), particularly the soybean-derived Bowman-Birk inhibitor, have proved to be powerful blockers of carcinogenesis in many in vitro and animal model systems. However, so far an ability of PIs to suppress gastric carcinogenesis has not been demonstrated, because of the anticipated 'hostile' acidic gastric environment for the PI to exert its action. We therefore examined the ability of a purified PI from the Indian legume the field bean (FBPI), when administered by gavage, to subdue benzopyrene (BP)-induced neoplasia of the forestomach of mice. Forestomach tumors were produced in female Swiss albino mice by oral administration of BP at a dose of 1 mg twice weekly for 4 weeks. Groups of mice were treated per os with an aqueous solution of FBPI for 3 months or more at a dose of 20 mg/kg once daily, six times a week, either from the initiation of carcinogenesis or after completion of the carcinogen treatment. Another group was treated likewise with autoclaved inactive FBPI. Mice of both the FBPI-treated groups showed statistically significant (P < 0.001) reductions in the multiplicity of gastric tumors, with the tumor incidence being unaffected. However, the suppression of tumor multiplicity was appreciably (P < 0.01) more in the group that received FBPI treatment concomitantly with the carcinogen. The mice that were treated with heat-inactivated FBPI showed similar tumor multiplicity to the BP-treated group, indicating that the oncopreventive activity of FBPI is related to its protease inhibitory capacity. These observations point to the potential of PIs as effective chemoprotectors against gastric cancer in animals and, possibly, in humans as well.