Effects Of Bowman-Birk Inhibitor Research Articles

The Effect of Bowman-Birk Inhibitor from Soybeans on the Sensitivity of Prostate Cancer Stem-like Cells to Anti-androgen Agent

The Effect of Bowman-Birk Inhibitor from Soybeans on the Sensitivity of Prostate Cancer Stem-like Cells to Anti-androgen Agent

Bowman-Birk inhibitor modifies transcription of autophagy and apoptosis genes in an in vitro model of Alzheimer's disorder.

Alzheimer, a current neurodegenerative disorder has adverse effects on memory and behavior. β-Amyloid peptide accumulations are the hallmarks of Alzheimer. Dysfunction of autophagy and apoptosis is detected in Alzheimer's disease. The effect of Bowman-Birk inhibitor (BBI), purified from soybean, was investigated in autophagy and apoptosis in Alzheimer treatment. Treated-PC12 cells with 1000 nM HgCl2 induced amyloid β (Aβ) accumulation. Treatment of PC12 cells with 1000 nM HgCl 2 and then 500 μg/mL BBI could decrease the expression ratio of Bax/Bcl2 and increase the expression of beclin1, Bnip3, Atg5, and autophagy-related genes. These results indicated that BBI could inhibit Aβ accumulation by inducing autophagy, and also the neuroprotective effect was detected through decreasing apoptosis in the in vitro model of Alzheimer's disease. These results provided further evidence for the potential effectiveness of BBI in the treatment of Alzheimer's disease.

Bowman–Birk inhibitor suppresses autoimmune inflammation and neuronal loss in a mouse model of multiple sclerosis

The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor. BBI concentrate (BBIC) is an extract enriched with BBI, but predominantly contains other ingredients including several protease inhibitors. We previously found that BBIC administration to Lewis rats with experimental autoimmune encephalomyelitis (EAE) significantly suppresses disease. In the present study we determined whether BBI mediates the suppressive effects of BBIC in EAE, evaluated its potential neuroprotective effects, and investigated mechanisms of BBI action. We tested effects of purified BBI on clinical and histopathological parameters of EAE in two models (relapsing/remitting EAE in SJL/J mice and chronic EAE in C57BL/6 mice). Effects of BBI were compared to BBIC in relapsing/remitting EAE, and effects of BBI on neuronal survival were examined during acute optic neuritis. Treatment with BBI in both EAE models significantly improved EAE disease parameters (onset, severity, weight loss, inflammation and demyelination). BBI significantly reduced the incidence of optic neuritis and prevented loss of retinal ganglion cells. In most experiments proliferation of immune cells derived from BBI-treated mice was significantly lower relative to control groups. Using Boyden's chamber assay we found that BBI inhibited invasiveness of activated splenocytes through the matrigel barrier. BBI also induced higher production of EAE-suppressive cytokine IL-10 by immune cells. These results demonstrate that BBI is the active component of BBIC that ameliorates clinical EAE. BBI reduces inflammation and attenuates neuronal loss, making it an excellent candidate for oral therapy in MS. BBI likely ameliorates EAE by inhibiting multiple pathways involved in disease pathogenesis.

Protection against Adverse Biological Effects Induced by Space Radiation by the Bowman-Birk Inhibitor and Antioxidants

This study was undertaken to evaluate the protective effects of the soybean-derived Bowman-Birk inhibitor (BBI), BBI concentrate (BBIC) and/or antioxidants against the adverse biological effects induced by space radiation in cultured human epithelial cells. The effects of BBI, BBIC and a combination of ascorbic acid, co-enzyme Q10, L-selenomethionine (SeM) and vitamin E succinate on proton and HZE-particle [high-energy (high E) nuclei of heavier (high atomic number, Z) elements] radiation-induced cytotoxicity in MCF10 human breast epithelial cells and a phenotypic change associated with transformation in HTori-3 human thyroid epithelial cells were assessed with a clonogenic survival assay and a soft agar colony formation assay. The results demonstrate that BBIC and antioxidants are effective in protecting against space radiation-induced cytotoxicity in MCF10 cells and BBI, BBIC and antioxidants are effective in protecting against a space radiation-induced phenotypic change associated with transformation of HTori-3 cells.

Restoration of connexin 43 by Bowman-Birk protease inhibitor in M5076 bearing mice

The present study was designed to investigate the effects of Bowman-Birk inhibitor (BBI) on up-regulation of connexin (Cx) expression to estimate BBI's tumor-suppressor effect in mice with M5076 ovarian sarcoma. The relative tumor weight (p<0.05, r(2)=0.301) and proliferating cell nuclear antigen (PCNA, p<0.01, r(2)=0.493) were negatively correlated with the doses of BBI. In contrast, the relative density of Cx43 was positively correlated with the doses of BBI (p<0.05, r(2)=0.351). Therefore, it suggests that the anti-carcinogenic effects of BBI induced negative growth control caused by the expression of Cx43 genes in mice with M5076 ovarian sarcoma.

Effects of Bowman-Birk Inhibitor on Rat Colon Carcinogenesis

The present study was undertaken to determine whether the Bowman-Birk inhibitor (BBI) could prevent colon carcinogenesis in rats treated with dimethylhydrazine (DMH) and whether there were adverse side effects associated with treatment with BBI for cancer prevention. BBI was evaluated in the forms of purified BBI (PBBI) or an extract of soybeans enriched in BBI, termed BBI concentrate (BBIC). The results demonstrate that PBBI and BBIC reduced the incidence and frequency of tumors in DMH-treated rats compared with animals treated with DMH alone. Autoclaved BBIC, in which the protease inhibitor activity of BBI was destroyed, had a weak and statistically insignificant, suppressive effect on DMH-induced colon carcinogenesis in rats, suggesting that the protease inhibitor activity of BBI is likely to be responsible for the anticarcinogenic activity of BBIC. Soy molasses, which contains soy isoflavones, did not have an effect on colon cancer carcinogenesis in DMH-treated rats. Similar to results from previous studies (Nauss et al. JNCI 73, 915-924, 1984), the most aggressive, malignant colon adenocarcinomas developed within or in association with gut-associated lymphoid tissue aggregates. No adverse side effects on the pancreas or animal growth were observed in rats treated with PBBI or BBIC. These results demonstrate that PBBI and BBIC may be used to prevent colon cancer without significant adverse side effects.

Effects of the Bowman-Birk inhibitor on growth, invasion, and clonogenic survival of human prostate epithelial cells and prostate cancer cells.

The Bowman-Birk inhibitor (BBI) is a soybean-derived serine protease inhibitor with demonstrated anticarcinogenic activity in both in vitro and in vivo systems. The effects of BBI and BBI Concentrate (BBIC), a soybean concentrate enriched in BBI, on cell growth, invasion, and/or survival were evaluated by the sulforhodamine B assay, a colony formation assay, the trypan blue dye exclusion assay and an in vitro invasion assay. The cells used in these studies were normal human prostate epithelial cells and prostate epithelial cell lines derived from embryonic prostate tissue (267B1) or benign prostatic hyperplasia (BPH) tissue (BRF-55T) and human prostate cancer cells established by Ki-ras oncogene transfection of 267B1 cells (267B1/Ki-ras) or from metastatic lesions of human prostate cancer (LNCaP and PC-3). BBIC had a statistically significant inhibitory effect on the growth and clonogenic survival of BRF-55T, 267B1/Ki-ras, LNCaP, and PC-3 cells. BBI also inhibited the growth of LNCaP cells and the clonogenic survival of BRF-55T and 267B1/Ki-ras cells and decreased the ability of LNCaP cells to invade across reconstituted basement membrane (Matrigel) when PC-3 cell-conditioned medium was utilized as the chemoattractant. BBI or BBIC did not affect the growth of normal prostate epithelial cells. BBI and/or BBIC could be a useful agent for treatment of prostate diseases.

Effects of the Bowman-Birk Inhibitor on Clonogenic Survival and Cisplatin- or Radiation-Induced Cytotoxicity in Human Breast, Cervical, and Head and Neck Cancer Cells

Bowman-Birk inhibitor (BBI) is a soybean-derived anticarcinogenic protease inhibitor previously shown to potentiate cisplatin-induced cytoxicity in human lung and ovarian cancer cells. To further assess the potential of BBI as a sensitizing agent for cancer radiotherapy and chemotherapy, we evaluated the effects of BBI and a soybean concentrate enriched in BBI known as BBI concentrate (BBIC) on clonogenic survival and radiation- or cisplatin-induced cell killing in MCF7 human breast carcinoma cells, SCC61 and SQ20B human head and neck carcinoma cells, HeLa, HeLa-R1, and HeLa-R3 human cervical carcinoma cells, MCF10 nontumorigenic human epithelial cells, HTori-3 nontumorigenic human thyroid epithelial cells, and C3H10T1/2 mouse fibroblast cells. BBI and BBIC significantly suppressed the clonogenic survival of MCF7 and SCC61 cells. BBIC also suppressed the survival of SQ20B cells and enhanced radiation-induced cell killing in SCC61 and SQ20B cells and cisplatin-induced cell killing in HeLa, HeLa-R1, and HeLa-R3 cells. In contrast, BBI and/or BBIC did not enhance radiation-induced cell killing in MCF10 cells or cisplatin-induced cell killing in C3H10T1/2 cells. BBI did not significantly affect the survival of SQ20B cells or enhance radiation-induced cell killing in SCC61 and SQ20B cells. The clonogenic survivals of MCF10 and C3H10T1/2 cells were not adversely affected by treatment with BBI or BBIC. The clonogenic survival of HTori-3 cells was only moderately suppressed by treatment with BBIC at ≥80 mg/ml. These results suggest that BBIC could be a useful agent for the potentiation of radiation- and cisplatin-mediated cancer treatment without significant adverse effects on surrounding normal tissues.

Protease inhibitors suppress in vitro growth of human small cell lung cancer

The effect of the protease inhibitors Bowman Birk inhibitor (BBI) and aprotinin on the in vitro clonal growth of two human small cell lung cancer (SCLC) cell lines was investigated. In addition, the effect of BBI on the growth factor processing of proGRP by SCLC cells and on mRNA levels for prohormone convertase 1 and 2 (PC1 and PC2) in SCLC cells was examined. The protease inhibitors BBI and aprotinin significantly decreased growth in both SCLC cell lines studied. In NCI-H345 cells, BBI appears to inhibit the processing of proGRP to GRP, as indicated by Western blot analysis. NCI-H345 cells, when treated with BBI (100 μg/ml), also showed highly significant decreases of mRNA for PC1 and PC2 of about 50%. These data suggest that proteases serve an important role in the growth regulation of SCLC and that inhibitors of these proteases may be potent suppressors of SCLC growth at the level of the gene.