A Mini Review on New Pharmacological and Toxicological Considerations of Protease Inhibitors' Application in Cancer Prevention and Biological Research

Rahimi, Hamid Reza; Hasanli, E.; Jamalifar, Hossein

doi:10.3923/ajcb.2012.1.12

Cited by 3 publications

(1 citation statement)

References 51 publications

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“…For example, the ChemBridge compound 5109870 which had the lowest activity score difference (−10.16) and was ranked tenth by the connectivity has been found previously to induce HIF-1α-responsive genes, chelate iron, and block progression of BC in two distinct mouse models [ 36 ]. MG-132 and MG-262 are proteasome inhibitors which have been shown in vitro and in vivo to have anticancer properties on their own, or synergistically with other compounds [ 37 ]. In one study, the combination of natural compounds such as gambogic acid with MG-132 or MG-262 showed inhibitory effects on growth of malignant cells and tumors in allograft animal models apparently with no observed systemic toxicity [ 38 ].…”

Section: Discussionmentioning

confidence: 99%

Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer

Huang

Lakowski

2022

Pharmacogenomics J

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Our previous studies demonstrated that the FOXM1 pathway is upregulated and the PPARA pathway downregulated in breast cancer (BC), and especially in the triple negative breast cancer (TNBC) subtype. Targeting the two pathways may offer potential therapeutic strategies to treat BC, especially TNBC which has the fewest effective therapies available among all BC subtypes. In this study we identified small molecule compounds that could modulate the PPARA and FOXM1 pathways in BC using two methods. In the first method, data were initially curated from the Connectivity Map (CMAP) database, which provides the gene expression profiles of MCF7 cells treated with different compounds as well as paired controls. We then calculated the changes in the FOXM1 and PPARA pathway activities from the compound-induced gene expression profiles under each treatment to identify compounds that produced a decreased activity in the FOXM1 pathway or an increased activity in the PPARA pathway. In the second method, the CMAP database tool was used to identify compounds that could reverse the expression pattern of the two pathways in MCF7 cells. Compounds identified as repressing the FOXM1 pathway or activating the PPARA pathway by the two methods were compared. We identified 19 common compounds that could decrease the FOXM1 pathway activity scores and reverse the FOXM1 pathway expression pattern, and 13 common compounds that could increase the PPARA pathway activity scores and reverse the PPARA pathway expression pattern. It may be of interest to validate these compounds experimentally to further investigate their effects on TNBCs.

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Section: Discussionmentioning

confidence: 99%

Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer

Huang

Lakowski

2022

Pharmacogenomics J

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Screening Combinatorial Peptide Libraries in Protease Inhibitor Drug Discovery

Poręba

Kasperkiewicz

Rut

et al. 2018

Extracellular Targeting of Cell Signaling in Cancer

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Plant-Derived Protease Inhibitors LC-pi (Lavatera cashmeriana) Inhibit Human Lung Cancer Cell Proliferation In Vitro

Rakashanda

Qazi

Majeed

et al. 2014

Nutrition and Cancer

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The objective of this study was to check the anticancer activity of purified protease inhibitors of Lavatera cashmeriana viz LC-pi I, II, III, and IV (Lavatera cashmeriana protease inhibitors) on A549 (lung) cell. It was found that LC-pi I and II significantly inhibited the proliferation of A549 cells with IC₅₀ value of 54 μg/ml and 38 μg/ml, respectively, whereas inhibition by LC-pi III and IV was negligible. LC-pi I and II were further found to inhibit formation of colonies in a dose-dependent manner. Also, both inhibitors were found to induce apoptosis causing chromatin condensation and DNA fragmentation, without loss of mitochondrial membrane potential. Cell cycle revealed a significant increase of subG₀/G₁ phase cells that are apoptotic cells. We also demonstrated a dose-dependent decrease in migration of A549 cells on cell migration assay by both inhibitors. Taken together, we demonstrate that LC-pi I and II inhibited proliferation through arresting cells before apoptosis, inducing apoptosis and inhibiting cell migration in human lung cancer cells, but the study warrants further investigation. Our results support the notion that plant protease inhibitors may have the potential to advance as chemopreventive agents.

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A Mini Review on New Pharmacological and Toxicological Considerations of Protease Inhibitors' Application in Cancer Prevention and Biological Research

Cited by 3 publications

References 51 publications

Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer

Bioinformatics driven discovery of small molecule compounds that modulate the FOXM1 and PPARA pathway activities in breast cancer

Screening Combinatorial Peptide Libraries in Protease Inhibitor Drug Discovery

Plant-Derived Protease Inhibitors LC-pi (Lavatera cashmeriana) Inhibit Human Lung Cancer Cell Proliferation In Vitro

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