Role of protease and protease inhibitors in cancer pathogenesis and treatment

Eatemadi, Ali; Aiyelabegan, Hammed Tanimowo; Negahdari, Babak; Mazlomi, Mohammad Ali; Daraee, Hadis; Daraee, Nasim; Eatemadi, Razieh; Sadroddiny, Esmaeil

doi:10.1016/j.biopha.2016.12.021

Cited by 120 publications

(82 citation statements)

References 95 publications

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“…Proteases are enzymes that hydrolyze peptide bonds and are named based on the amino acid involved in the active site of the enzyme. Proteases play a role in tumor growth in cancer . Downregulation of serine protease HTRA has been reported previously in BC.…”

Section: Resultsmentioning

confidence: 77%

Comparative two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) of human milk to identify dysregulated proteins in breast cancer

et al. 2018

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Breast cancer (BC) remains a major cause of mortality, and early detection is considered important for reducing BC-associated deaths. Early detection of BC is challenging in young women, due to the limitations of mammography on the dense breast tissue of young women. We recently reported results of a pilot proteomics study, using one-dimensional polyacrylamide gel electrophoresis (1D-PAGE) and mass spectrometry (MS) to investigate differences in milk proteins from women with and without BC. Here, we applied two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) and MS to compare the protein pattern in milk from the breasts of a single woman who was diagnosed with BC in one breast 24 months after donating her milk. Statistically different gel spots were picked for protein digestion followed by nanoliquid chromatography tandem MS (nanoLC-MS/MS) analysis. The upregulated proteins in BC versus control are alpha-amylase, gelsolin isoform a precursor, alpha-2-glycoprotein 1 zinc isoform CRA_b partial, apoptosis-inducing factor 2 and vitronectin. Several proteins were downregulated in the milk of the breast later diagnosed with cancer as compared to the milk from the healthy breast, including different isoforms of albumin, cholesterol esterase, different isoforms of lactoferrin, different proteins from the casein family and different isoforms of lysozyme. Results warrant further studies to determine the usefulness of these milk proteins for assessing risk and detecting occult disease. MS data is available via ProteomeXchange with identifier PXD009860.

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Section: Resultsmentioning

confidence: 77%

Comparative two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) of human milk to identify dysregulated proteins in breast cancer

et al. 2018

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“…The imbalance between cysteine proteases and cystatins may be clinically useful in combatting cancer [11, 47]. Therefore, cystatins could be considered a potential therapeutic strategy for cancer [8]. In the present study, the small bioactive molecule RHcyst-1 from tick belonging to the type 1 cystatin family has been proven to have effective antitumor activity in vitro and in vivo .…”

Section: Discussionmentioning

confidence: 90%

“…Cathepsins, such as cathepsins B, H, K, and L, belong to the family of cysteine proteases that have been associated with cancer progression, tumor burden, overall survival, tumor cell proliferation, angiogenesis, and metastasis [4-7]. Cathepsins are involved in different cancers and exhibit various characteristics and functions [8-17]. Serum cathepsin levels can be used as prognostic markers for melanoma [18].…”

Section: Introductionmentioning

confidence: 99%

A Tick Cysteine Protease Inhibitor RHcyst-1 Exhibits Antitumor Potential

Wei

Wang

et al. 2018

Cell Physiol Biochem

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Background/Aims: We previously identified a potent and tight-binding inhibitor of cysteine proteases from Rhipicephalus haemaphysaloides, RHcyst-1, which belongs to the cystatin type 1 family. Cathepsins, which are members of the cysteine protease family, participate in various pathological processes, including the initiation and development of cancers. The present study aimed to investigate the antitumor effects of RHcyst-1 and to explore the underlying mechanism of these effects. Methods: Different tumor cells were treated with RHcyst-1 in vitro. Proliferation activity was evaluated using Cell Counting Kit-8, and migration and invasion were determined by wound healing and Transwell® invasion assays. In addition, a mouse tumor therapy model was established by inoculating the left forelimb of mice with B16-F10 cells, and tumor progression was evaluated by assessing tumor volume and survival. Flow cytometry was conducted to evaluate myeloid-derived suppressor cells (MDSCs), CD4⁺, and CD8⁺ T cell levels in PBMCs and spleens. Immunohistochemistry was performed to analyze immune cell infiltration and angiogenesis in the tumors. Results: RHcyst-1 significantly inhibited the proliferation, migration, and invasion of all four different tumor cells in vitro. Additionally, it inhibited tumor growth and improved survival in vivo. A decrease and an increase in MDSCs levels were observed in PBMCs and in the spleen, respectively, after RHcyst-1 application. Conclusions: Tick RHcyst-1 has potential antitumor efficacy, and the observed antitumor activities may be partly attributable to changes in cathepsin expression and MDSCs levels in the PBMCs and spleens. The findings of the present study suggest that RHcyst-1 may have the potential to be utilized in cancer treatment.

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“…Their deregulation is implicated in many diseases including cancer, neurodegeneration, and inflammation . Thus, many efforts have been made to develop serine proteases inhibitors . In such a context, fluorescence spectrometry is a lead technique to identify and characterize inhibitors.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] Thus, many efforts have been made to develop serine proteases inhibitors. [4][5][6][7] In such a context, fluorescence spectrometry is a lead technique to identify and characterize inhibitors. Fluorescence assays are based on the use of peptide substrates bearing fluorogenic groups that generate highly fluorescent entities during hydrolytic digestion.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Peptide–Adenine Conjugates as a New Tool for Monitoring Protease Activity

Masurier

Soualmia²,

Sanchez

et al. 2018

Eur J Org Chem

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We took advantage of the powerful adenine SERS (Surface Enhanced Raman Spectroscopy) probe to design peptide–adenine conjugates as candidates for use as serine protease substrates. Whereas the direct introduction of the peptide sequence on the adenine exocyclic N6 amine gave an imidazopurinone derivative, the introduction of an aminoethyl linker between the adenine group and the peptide chain led to the expected candidate probes. These potential substrates were then evaluated for monitoring the hydrolytic activity of trypsin, used as a model protease, by HPLC and by SERS. We demonstrated that the Boc–VPR–adenine conjugate is a substrate of trypsin and constitutes a good starting point to design optimized substrates to monitor protease activity by SERS.

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Role of protease and protease inhibitors in cancer pathogenesis and treatment

Cited by 120 publications

References 95 publications

Comparative two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) of human milk to identify dysregulated proteins in breast cancer

Comparative two‐dimensional polyacrylamide gel electrophoresis (2D‐PAGE) of human milk to identify dysregulated proteins in breast cancer

A Tick Cysteine Protease Inhibitor RHcyst-1 Exhibits Antitumor Potential

Synthesis of Peptide–Adenine Conjugates as a New Tool for Monitoring Protease Activity

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