Soybean Bowman-Birk Protease Inhibitor (BBI): Identification of the Mechanisms of BBI Suppressive Effect on Growth of Two Adenocarcinoma Cell Lines: AGS and HT29

Fereidunian, Amirhossein; Sadeghalvad, Mona; Oscoie, Maryam Omidi; Mostafaie, Ali

doi:10.1016/j.arcmed.2014.07.001

Cited by 26 publications

(24 citation statements)

References 20 publications

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“…Several studies point to the fact that MMP activity inhibition appears to be a promising anticancer therapy [10,79]. Within MMPs, MMP-9 is the most studied because of their importance in cell migration, angiogenesis and metastasis formation [33,80]. Hence, we further set out to analyze the extracts’ specific activity towards MMP-9 enzymes, in their determined IC 50 concentrations, using the DQ-gelatin assay.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, previous studies have shown greater cytotoxic effects induced by saponins and phenolics. For example, Fereidunian et al [33] found that 200 μg/mL of soybean BBI did decrease cell multiplication at a concentration of 400 μg/mL in HT29 cells. However, these works involved specific isolated molecules, and in higher concentrations.…”

Section: Resultsmentioning

confidence: 99%

“…It is known that MMP inhibitors may have an action at different molecular levels: (i) inhibition of transcription; (ii) inhibition of post-transcription; (iii) inhibition of translation; (iv) post-translational degradation; and (v) inhibition of secretion or activity [33]. In this case, inhibition of active MMP-9 may have been achieved either by a direct inhibition of MMP-9 expression or activity, since there was also a decrease in pro-MMP-9.…”

Section: Resultsmentioning

confidence: 99%

“…The peptide lunasin, a small subunit derived from the larger cotyledon-specific 2S seed albumin, also has both anticancer and anti-inflammatory activities [30]. Thus far, soy isoflavones and saponins are the only two bioactive compounds in soy that were shown to be effective MMP inhibitors [31], whilst BBIs were shown to be more likely involved in suppressing the production of superoxide anion free radicals, targeting cancer cells, or suppressing their growth [25,29,32,33,34,35]. Lunasin, according to Kyle et al [36], does not have a role in MMP inhibition as well, but rather, it involves physical interactions with chromatin and histones [37].…”

Section: Introductionmentioning

confidence: 99%

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Proteins in Soy Might Have a Higher Role in Cancer Prevention than Previously Expected: Soybean Protein Fractions Are More Effective MMP-9 Inhibitors Than Non-Protein Fractions, Even in Cooked Seeds

et al. 2017

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The search for anticancer MMP-9 inhibitors (MMPIs) in food products has become a major goal for research. MMPIs in soy have been related only to saponins and isoflavones, but recently, low specific protein fractions in soybeans were shown to reduce MMP-9 activity as well. The present work aimed at comparing the MMPI potential of protein fractions (P) and non-protein fractions (NP) isolated from soybean seeds, before and after soaking and cooking, mimicking dietary exposures. Reverse and substrate zymography, as well as a fluoregenic DQ gelatin assay were used to evaluate MMP-9 activities. Colon cancer cell migration and proliferation was also tested in HT29 cells. Regarding MMP-9 inhibition, proteins in soy presented IC50 values 100 times lower than non-protein extracts, and remained active after cooking, suggesting that proteins may be more effective MMP-9 inhibitors than non-protein compounds. Using the determined IC50 concentrations, NP fractions were able to induce higher inhibitions of HT29 cell migration and proliferation, but not through MMP-9 inhibition, whilst protein fractions were shown to specifically inhibit MMP-9 activity. Overall, our results show that protein fractions in soybeans might have a higher role in soy-related cancer prevention as MMPIs than previously expected. Being nontoxic and active at lower concentrations, the discovery of these heat-resistant specific MMPI proteins in soy can be of significant importance for cancer preventive diets, particularly considering the increasing use of soy proteins in food products and the controversy around isoflavones amongst consumers.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Proteins in Soy Might Have a Higher Role in Cancer Prevention than Previously Expected: Soybean Protein Fractions Are More Effective MMP-9 Inhibitors Than Non-Protein Fractions, Even in Cooked Seeds

et al. 2017

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“…These two soybean‐derived molecules are also well‐known to have various anticancer and immunomodulating activities in vitro and in vivo . We recently reported the suppressive effect of BBI on growth of the two adenocarcinoma cell lines: AGS and HT29 . Despite the report of Dia et al about synergistic effects of these two compounds in suppressing the nitric oxide and prostaglandin E2 pathways in LPS‐induced macrophages and depression of serum levels of TNF‐α in the LPS‐induced mice by genistein, in vivo protective effect of combination of these two compounds against inflammation has not been yet reported.…”

Section: Introductionmentioning

confidence: 93%

In vivo anti‐inflammatory efficacy of the combined Bowman‐Birk trypsin inhibitor and genistein isoflavone, two biological compounds from soybean

Sadeghalvad

Mohammadi-Motlagh

Karaji

et al. 2019

J Biochem & Molecular Tox

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Soybean Bowman‐Birk protease inhibitor (BBI) and genistein, two biological compounds from soybean, are well‐known for their anti‐inflammatory, antioxidant, and anticancer activities. The aim of this study was designing a BBI‐genistein conjugate and then investigating its protective effect on lipopolysaccharide (LPS)‐induced inflammation in BALB/c mice, compared with the effects of combination of BBI and genistein. BBI was purified from soybean and the BBI‐genistein conjugate was synthesized. The BALB/c mice were intraperitoneally treated 2 hours before LPS induction. Our results showed that treatment with the combination of BBI and genistein greatly led to more reduced serum levels of tumor necrosis factor (TNF)‐α and interferon (IFN)‐γ compared with the treatments of BBI alone, the BBI‐genistein conjugate, and genistein alone, respectively. Moreover, the expression of TNF‐α and IFN‐γ in the splenocytes was significantly downregulated along with improving host survival against the LPS‐induced lethal endotoxemia in the same way. Our data support a new combined therapy using BBI and genistein, as natural anti‐inflammatory agents, to develop a new drug for inflammatory diseases.

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

Akbari

Akrami

Mostafaei

et al. 2019

J of Cellular Biochemistry

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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 HgCl 2 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. K E Y W O R D Samyloid β, apoptosis, autophagy, Bowman-Birk inhibitor, rat pheochromocytoma cells

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Soybean Bowman-Birk Protease Inhibitor (BBI): Identification of the Mechanisms of BBI Suppressive Effect on Growth of Two Adenocarcinoma Cell Lines: AGS and HT29

Cited by 26 publications

References 20 publications

Proteins in Soy Might Have a Higher Role in Cancer Prevention than Previously Expected: Soybean Protein Fractions Are More Effective MMP-9 Inhibitors Than Non-Protein Fractions, Even in Cooked Seeds

Proteins in Soy Might Have a Higher Role in Cancer Prevention than Previously Expected: Soybean Protein Fractions Are More Effective MMP-9 Inhibitors Than Non-Protein Fractions, Even in Cooked Seeds

In vivo anti‐inflammatory efficacy of the combined Bowman‐Birk trypsin inhibitor and genistein isoflavone, two biological compounds from soybean

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

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