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

Abstract

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.

Combined subcarcinogenic benzo[a]pyrene and UVA synergistically caused high tumor incidence and mutations in H‐ras gene, but not p53, in SKH‐1 hairless mouse skin

“…The total dose of BaP (0.6 lmol) with which mice were treated is only about 2% of the reported BaP carcinogenic dose, 23.8 and 31.7 lmol, respectively, used in other studies. 26,27 The doses of BaP and UVA employed in our study were at subcarcinogenic levels, as evidenced by the fact that neither UVA nor BaP alone induced any tumors in SKH-1 mice (Fig. 1), though gene mutation was detected in the nontumor skin of BaP-and UVAtreated mice after 10 weeks (Fig.…”

Isolation and Characterization of a Trypsin-Chymotrypsin Inhibitor from the Seeds of Green Lentil (Lens culinaris)

“…The suppressive action of protease inhibitors on tumor cells in vitro [45] and tumors in vivo [34][35][36][37][38][39][40][41][42] has been demonstrated.…”

“…Among the three types, Kunitz inhibitors are the largest with a molecular means of about 20 kDa while squash inhibitors are the smallest with a molecular mass of approximately 3 kDa. These protease inhibitors are known for their antitumor and anti-pest activities [29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45]. Protease inhibitors are also produced by animals [46].…”

Biological Significance of Polymorphism in Legume Protease Inhibitors from the Bowman-Birk Family

“…These effects were not observed when BBI was autoclaved, suggesting that protease inhibitor activity was necessary for its anti-carcinogenic properties. BBI-like proteins from field beans have proven to be biologically active, under acidic conditions, in suppressing benzopyreneinduced forestomach carcinogenesis following oral treatment in mice [64]. In addition, BBI has been reported to be distributed widely throughout the body following oral administration in mice [62], suggesting that it could exert chemopreventive activity in other organs and tissues, following transport as biologically active peptides.…”

“…One such candidate is matriptase (MT-SP1), a member of the class of type II transmembrane serine proteases, which exhibits trypsin-like protease activity and has been described in a variety of epithelial cancer cell lines [72]. MT-SP1 is implicated in BBI-like (field bean) benzopyrene mouse stomach carcinogenesis Fernandes and Banerji [64] Adapted from Clemente and Domoney [143].…”