8: Prostate 1983;4(4):345-9 Protease inhibitors: possible anticarcinogens in edible seeds. Troll W, Wiesner R. Protease inhibitors, which are common constituents of seeds (rice, beans, and maize) have been shown to inhibit breast, colon, and skin cancers in animal experiments. Epidemiological studies have shown that diets rich in these components (ie seed proteins) decrease the occurrence of prostatic, breast, and colon cancers in man. We have demonstrated that a typical purified inhibitor from soybeans, the Bowman-Birk inhibitor, is excreted in the feces complexed with digestive proteases from the duodenum. This results in greater excretion of proteins, thus effectively decreasing the amount of protein available for digestion. Excess protein in the diet in addition to fats may contribute to increased cancer. Thus, the addition of seeds (chick-peas, beans, etc) to the diet rather than removal of meat or fat offers the opportunity of preventing these cancers, because the protease inhibitors present would effectively remove a portion of the proteins being consumed. Protease inhibitors also act directly as antioxidants in relation to tumor promoters and ionizing radiation. To what extent this contributes to the nutritional effects of eating seeds containing protease inhibitors remains to be determined. PMID: 6346296 [PubMed - indexed for MEDLINE]
1: Cancer Invest 1996;14(6):597-608 Protease inhibitors and carcinogenesis: a review. Clawson GA. Department of Pathology, Milton S. Hershey Medical Center, Pennsylvania State University, Hershey 17033, USA. This brief review article deals with the subject of anticarcinogenic activity of protease inhibitors (PI). Three basic premises are made: (1) Although PI are prevalent constituents of dietary staples such as soy products, which have been epidemiologically associated with reduced cancer incidences at multiple target sites, they are unlikely to be the active anticarcinogenic entities. Cooked soy products, which are devoid of PI activity, are equally as effective at reducing cancer development as raw soy products. Isoflavones are likely to represent major chemopreventive agents in soy, although other constituents may well contribute. (2) Although supplementation of diets with PI (natural or synthetic), or direct topical administration, results in lower cancer incidences in many experimental models in vivo, this effect appears to be indirect. Dietary PI are, in general, poorly absorbed from the GI tract, and never reach target organs in any measurable quantity. The most attractive hypothesis is that dietary PI could induce synthesis and distribution of endogenous PI (acute-phase reactants), which have widespread effects on cell growth and behavior. Effects of topical administration of PI also encompass prominent anti-inflammatory effects. (3) A spectrum of PI inhibit in vitro transformation induced by a variety of carcinogenic agents. Their effects can be grouped into three basic categories, affecting: (a) signal transduction pathways; (b) DNA repair processes; and (c) nuclear proteases. I suggest that the nuclear multicatalytic protease activity, in particular the chymotrypsin-like activity, represents an important cellular target for which considerable anecdotal support can be garnered. Publication Types: Review Review, tutorial PMID: 8951363 [PubMed - indexed for MEDLINE]
2: Carcinogenesis 1995 Aug;16(8):1843-6 Inhibition of benzopyrene-induced forestomach tumors by field bean protease inhibitor(s). Fernandes AO, Banerji AP. Biological Chemistry Division, Cancer Research Institute, Parel, Bombay, India. 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. PMID: 7634412 [PubMed - indexed for MEDLINE]
1: J Physiol Biochem 2000 Sep;56(3):283-94 The role of phytic acid in legumes: antinutrient or beneficial function? Urbano G, Lopez-Jurado M, Aranda P, Vidal-Valverde C, Tenorio E, Porres J. Departamento de Fisiologia e Instituto de Nutricion y Tecnologia de Alimentos, Universidad de Granada. This review describes the present state of knowledge about phytic acid (phytate), which is often present in legume seeds. The antinutritional effects of phytic acid primarily relate to the strong chelating associated with its six reactive phosphate groups. Its ability to complex with proteins and particularly with minerals has been a subject of investigation from chemical and nutritional viewpoints. The hydrolysis of phytate into inositol and phosphates or phosphoric acid occurs as a result of phytase or nonenzymatic cleavage. Enzymes capable of hydrolysing phytates are widely distributed in micro-organisms, plants and animals. Phytases act in a stepwise manner to catalyse the hydrolysis of phytic acid. To reduce or eliminate the chelating ability of phytate, dephosphorylation of hexa- and penta-phosphate forms is essential since a high degree of phosphorylation is necessary to bind minerals. There are several methods of decreasing the inhibitory effect of phytic acid on mineral absorption (cooking, germination, fermentation, soaking, autolysis). Nevertheless, inositol hexaphosphate is receiving increased attention owing to its role in cancer prevention and/or therapy and its hypocholesterolaemic effect. Publication Types: Review Review literature PMID: 11198165 [PubMed - indexed for MEDLINE]