Pharmacomodulation of Broad Spectrum Matrix Metalloproteinase Inhibitors Towards Regulation of Gelatinases

Bourguet, Erika; Hornebeck, William; Sápi, János; Alix, Alain J. P.; Moroy, Gautier

doi:10.5772/35412

Cited by 6 publications

(10 citation statements)

References 83 publications

(70 reference statements)

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“…Since MMP-9 inhibitors (MMPIs) are considered anti-angiogenic agents and metastasis deterrents for colorectal cancer, and have also been demonstrated to effectively inhibit pre-cancer states such as colitis and other inflammatory bowel diseases [74]. In order to compare the MMP inhibitory potential of the protein and non-protein extracts from soybean seeds, and to select a concentration to use in the subsequent studies, we determined the half maximal effective inhibition of MMPs (IC 50 ) values for soluble protein (P) and non-protein (NP) fractions.…”

Section: Resultsmentioning

confidence: 99%

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%

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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“…In fact, A. vera was less effective in inhibiting cell invasiveness than A. arborescens . Other reports using different plant extracts with known MMP-9 inhibitory activities [ 16 , 17 , 20 , 30 , 46 – 48 ] showed similar results and a known MMP-9 inhibitor, doxycycline in the same conditions induced similar reductions in cell migration [ 40 ]. These results suggest that although A. vera is the most used species and has been attributed numerous therapeutic benefits, regarding anti-cancer potential, it may not be as efficient as it has been described in reducing cancer cell migration.…”

Section: Discussionmentioning

confidence: 52%

“…MMP-9 inhibitors (MMPIs) are considered metastasis deterrents and anti-angiogenic agents for colorectal cancer, and have also been proved to inhibit pre-cancerous states like colitis and other inflammatory bowel diseases [ 40 ]. Although many synthetic MMP inhibitors have been developed as potential anticancer drugs [ 40 , 41 ], because of MMP’s ubiquity, most trials were hampered by dose-limiting toxicity, insufficient clinical benefits and lack of specificity. Natural, plant and food-based MMP9 inhibitors are currently more preferable to these inhibitors because of their lack of side effects and potentially higher specificity.…”

Section: Discussionmentioning

confidence: 99%

Differential inhibition of gelatinase activity in human colon adenocarcinoma cells by Aloe vera and Aloe arborescens extracts

Lima

Batista-Santos

Veríssimo

et al. 2020

BMC Complement Med Ther

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Background Aloe’s reported bioactivities (anticancer, anti-inflammatory and wound healing) suggest they might inhibit a subgroup of matrix metalloproteinases (MMPs) called gelatinases (MMP-2 and MMP-9). The goal of the present study was to compare the MMP inhibitory potential of two Aloe species, A. vera and A. arborescens. Methods Different types of extraction were tested and specific bioactive compounds were quantified. Cancer cell invasion inhibitory activities were measured in vitro using the wound healing assay in human colon cancer cells (HT29). Effects on gelatinase activities were further assessed by dye-quenched gelatin and gelatin zymography. Results Different types of extraction yielded significantly different levels of bioactivities and of bioactive compounds, which might be due to a greater amount of extractable bioactive compounds such as anthraquinones. Both A. arborescens and A. vera have potential as inhibitory agents in cancer cell proliferation via MMP-9 and MMP-2 enzymatic activity inhibition, being able to reduce colon cancer cell proliferation and migration but A. arborescens showed to be a more effective inhibitor of cancer cell migration than A. vera. Conclusion This work opens novel perspectives on the mode of action of Aloe species in cancer cell migration and may provide clues as to why there are so many conflicting results on Aloe’s activities.

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“…It was demonstrated that these compounds were effective at inhibiting both the isolated SVMPs and the hemorrhagic activity of crude venoms in animal models 9,10 . Also, some hydroxamatecontaining tripeptides with sequence Phe-Leu-Phe showed good results in vitro 10,11 . Although hydroxamates are often pointed out as very potent SVMPs inhibitors, several challenges need to be addressed in the context of producing new drugs for these enzymes.…”

mentioning

confidence: 96%

“…By proposing inhibitors with more specific activity against the SVMPs some of the low-selectivity associated problems can be solved. But still, research has been so far focused mainly on highly efficient Zn 2+ ion binding groups 11,12 . Pharmacokinetics and toxicological issues of the potential inhibitors represent other problems that should be considered in the design of specific SVMPs inhibitors.…”

mentioning

confidence: 99%

Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests

Villalta-Romero

Borro

Mandić

et al. 2017

Bioorganic & Medicinal Chemistry Letters

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Snakebites represent an important public health problem, with a great number of victims with permanent sequelae or fatal outcomes, particularly in rural, agriculturally active areas. The snake venom metalloproteases (SVMPs) are the principal proteins responsible for some clinically-relevant effects, such as local and systemic hemorrhage, dermonecrosis, and myonecrosis. Because of the difficulties in neutralizing them rapidly and locally by antivenoms, the search and design of small molecules as inhibitors of SVMPs are proposed. The Bothrops asper metalloprotease P1 (BaP1) is hereby used as a target protein and by High Throughput Virtual Screening (HTVS) approach, the free access virtual libraries: ZINC, PubChem and ChEMBL, were searched for potent small molecule inhibitors. Results from the aforementioned approaches provided strong evidences on the structural requirements for the efficient BaP1 inhibition such as the presence of the pyrimidine-2,4,6-trione moiety. The two proposed compounds have also shown excellent results in performed in vitro interaction studies against BaP1.

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Pharmacomodulation of Broad Spectrum Matrix Metalloproteinase Inhibitors Towards Regulation of Gelatinases

Cited by 6 publications

References 83 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

Differential inhibition of gelatinase activity in human colon adenocarcinoma cells by Aloe vera and Aloe arborescens extracts

Discovery of small molecule inhibitors for the snake venom metalloprotease BaP1 using in silico and in vitro tests

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