Volume 86,
February 2017
, Pages 221-231
Author links open overlay panel, , , , , , ,
Abstract
Cancer is the second cause of death in 2015, and it has been estimated to surpass heart diseases as the leading cause of death in the next few years. Several mechanisms are involved in cancer pathogenesis. Studies have indicated that proteases are also implicated in tumor growth and progression which is highly dependent on nutrient and oxygen supply. On the other hand, protease inhibitors could be considered as a potent strategy in cancer therapy. On the basis of the type of the key amino acid in the active site of the protease and the mechanism of peptide bond cleavage, proteases can be classified into six groups: cysteine, serine, threonine, glutamic acid, aspartate proteases, as well as matrix metalloproteases. In this review, we focus on the role of different types of proteases and protease inhibitors in cancer pathogenesis.
Section snippets
Proteases
One of the most important biological catalytic reactions is proteolysis and this is known as proteolytic activity, which has been attributed to a class of enzymes called proteases. Proteolysis is the hydrolysis of peptide bond by attacking the carbonyl group of the peptide. Proteases are of broad enzymes distribution. In human, there are about 990 known protease genes. In addition, about 1605 known protease inhibitor genes have been reported in human [1].
On the basis of the nature of the key
The role of protease in cancer development
Proteases in normal cells are very essential in carrying out imperative biological processes, and can regulate a diversity of different cellular processes such as gene expression, differentiation, and cell death [6]. However, recent studies have indicated that proteases are also implicated in tumor growth and progression, both at primary and metastatic sites [3].
It has been shown, that tumor cells stimulate the expression of proteolytic enzymes in non-neoplastic neighboring cells, hijacking
Role of protease inhibitors in cancer treatment
While protease are involve in pathogenesis of cancer, protease inhibitors have been noted for their role in cancer therapy. However, protease inhibitor therapy design is complicated since different types of cancers use different proteases at the fluctuating stages of cancer development and no single inhibitor can be used on all classes of proteases [45], [46].
Conclusion
In this review, we provided an insight into the role of the protease and protease inhibitors in cancer. Proteases, are functionally involved in many processes of cancer progression, from benign to malignancy [4]. In cancer conditions, proteases were initially considered to stimulate cancer cell escape through tissue barriers. However, process of proteolysis is complicated in many aspects of cancer involving inflammatory cell recruitment, immune responses, proliferation, and apoptosis [10].
Conflict of interest
The authors declare no conflict of interest.
Acknowledgement
The authors thank Department of Medical Biotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran.
References (116)
- J. Kim et al.
Requirement for specific proteases in cancer cell intravasation as revealed by a novel semiquantitative PCR-based assay
Cell
(1998)
- S.D. Mason et al.
Proteolytic networks in cancer
Trends Cell Biol.
(2011)
- O. Vasiljeva et al.
Dual contrasting roles of cysteine cathepsins in cancer progression: apoptosis versus tumor invasion
Biochimie
(2008)
- K. Hirai et al.
Expression of cathepsin B and cystatin C in human colorectal cancer
Hum. Pathol.
(1999)
- N. Fujise et al.
Prognostic impact of cathepsin B and matrix metalloproteinase-9 in pulmonary adenocarcinomas by immunohistochemical study
(Video) Dr. Walter Schmidt discusses the different roles of proteases in cancerLung Cancer
(2000)
- J.M. Lankelma et al.
Cathepsin L, target in cancer treatment?
Life Sci.
(2010)
- Y.A. DeClerck et al.
Proteases, extracellular matrix, and cancer: a workshop of the path B study section
Am. J. Pathol.
(2004)
- G. Dodson et al.
Catalytic triads and their relatives
Trends Biochem. Sci.
(1998)
- S. Diment et al.
Cleavage of parathyroid hormone in macrophage endosomes illustrates a novel pathway for intracellular processing of proteins
J. Biol. Chem.
(1989)
- E. Liaudet-Coopman et al.
newly discovered functions of a long-standing aspartic protease in cancer and apoptosis
Cancer Lett.
(2006)
Protease inhibitors and their peptidomimetic derivatives as potential drugs
Pharmacol. Ther.
(2007)
Expression of cysteine peptidase cathepsin L and its inhibitors stefins A and B in relation to tumorigenicity of breast cancer cell lines
Cancer Lett.
(2002)
Serum cystatin C in patients with head and neck carcinoma
Clin. Chim. Acta
(2004)
Chrysin abrogates early hepatocarcinogenesis and induces apoptosis in N-nitrosodiethylamine-induced preneoplastic nodules in rats
Toxicol. Appl. Pharmacol.
(2011)
Serpins flex their muscle II. Structural insights into target peptidase recognition, polymerization, and transport functions
J. Biol. Chem.
(2010)
Serpins flex their muscle I. Putting the clamps on proteolysis in diverse biological systems
J. Biol. Chem.
(2010)
Serum prostate specific antigen complexed to alpha 1-antichymotrypsin as an indicator of prostate cancer
J. Urol.
(1993)
Usefulness of alpha 1-antichymotrypsin-PSA complex for predicting bone metastases of prostate cancer
Urology
(2006)
Gcet1 (centerin), a highly restricted marker for a subset of germinal center-derived lymphomas
Blood
(2008)
K.A. ten hoor, J.G., aalders, B.G., szabo, E.G. de vries, serum squamous cell carcinoma antigen and CYFRA 21-1 in cervical cancer treatment
Int. J. Radiat. Oncolo. Biol. Phys.
(2002)
Serum proteomics study of the squamous cell carcinoma antigen 1 in tongue cancer
Oral Oncol.
(2006)
The proteasome: structure, function, and role in the cell
Cancer Treat. Rev.
(2003)
Using the MEROPS database for proteolytic enzymes and their inhibitors and substrates
Curr. Protoc. Bioinf.
(2014)
Protease signalling: the cutting edge
EMBO J.
(2012)
Molecular imaging of proteases in cancer
Cancer Growth and Metastasis
(2009)
Complexity of cancer protease biology: cathepsin K expression and function in cancer progression
Semin. Cancer Biol.
(2015)
Enzymes/transporters, Molecular Imaging II
(2008)
New functions for the matrix metalloproteinases in cancer progression
Nat. Rev. Cancer
(2002)
Role of proteases in cancer: a review
Biotechnol. Mol. Biol. Rev.
(2012)
Critical appraisal of the use of matrix metalloproteinase inhibitors in cancer treatment
Oncogene
(2000)
Cysteine cathepsins: multifunctional enzymes in cancer
Nat. Rev. Cancer
(2006)
Cysteine cathepsins and the cutting edge of cancer invasion
ABBV Cell Cycle
(2007)
Cysteine cathepsins in human cancer
Biol. Chem.
(2004)
Cathepsin B inhibition interferes with metastatic potential of human melanoma: an in vitro and in vivo study
Mol. Cancer
(2010)
Multiple roles for cysteine cathepsins in cancer
ABBV Cell Cycle
(2004)
Lysosomal cathepsin B participates in the podosome-mediated extracellular matrix degradation and invasion via secreted lysosomes in v-Src fibroblasts
Cancer Res.
(2008)
Prognostic significance of immunohistochemical analysis of cathepsin D in low‐stage breast cancer
Cancer
(1993)
Targeting cathepsins: a new glimmer of hope for pancreatic cancer therapy?
Gut
(2012)
Cathepsin B and cysteine protease inhibitors in human tongue cancer: correlation with tumor staging and in vitro inhibition of cathepsin B by chicken cystatin
J. Cancer Mol.
(2006)
Expression of cysteine protease cathepsin L is increased in endometrial cancer and correlates with expression of growth regulatory genes
Cancer Invest.
(2012)
Serine protease mechanism and specificity
Chem. Rev.
(2002)
MEROPS: the peptidase database
Nucleic Acids Res.
(2000)
Purification of isoenzymes from human and chicken liver
Biochem. J.
(1970)
Pleiotropic effects of cathepsin D, Endocrine
Endocr. Metab. Immune Disord. Drug Targets
(2009)
The dilemma: does tissue expression of cathepsin D reflect tumor malignancy? The question: does the assay truly mirror cathepsin D mis-function in the tumor?
Cancer Biomark. Sect. A Dis. Mark.
(2009)
Matrix metalloproteinase-induced epithelial-mesenchymal transition in breast cancer
J. Mammary Gland Biol. Neoplasia
(2010)
Cathepsin-D, key protease in breast cancer, is up-regulated in obese mouse and human adipose tissue, and controls adipogenesis
PLoS One
(2011)
Clinical significance of cathepsin D concentration in tumor cytosol of primary breast cancer
Int. J. Biol. Mark.
(2004)
Ribozyme-targeting procathepsin D and its effect on invasion and growth of breast cancer cells: an implication in breast cancer therapy
Int. J. Oncol.
(2007)
Protein-mediated assembly of nanodiamond hydrogels into a biocompatible and biofunctional multilayer nanofilm
ACS Nano
(2008)
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Extraction of protein with protease inhibitor activity from Brazilwood (Caesalpinia echinata LAM.) seeds using choline-based ionic liquids
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Proteolytic inhibitors are low molecular weight proteins that prevent protein hydrolysis and are used against moderate to high severity diseases. Some plants can produce these protease inhibitors, such as Brazilwood seeds (Caesalpinia echinata LAM.). This work aimed to optimise the extraction of proteins from Brazilwood seeds with proteolytic inhibitory activity, using choline-based ionic liquid. The seeds were characterised in terms of their dimensions (15mm in length, 11mm in width and 4.8mm in thickness), centesimal composition (moisture - 9.21%, ash - 3.37%, lipids - 32.6%, total fibre - 0.80%, crude proteins - 17.2%, carbohydrates - 36.8%), energy (510Kcal.100g-1) and major fatty acid (linoleic acid - 43%). Protein extraction was performed by maceration of the Brazilwood seeds using ionic liquids (choline bitartrate, choline chloride and choline dihydrogen citrate) and optimised using a factorial design of experiments, whose variables were the temperature and solvent concentration, with the total protein content as the response variable. The best extraction conditions were 25.42°C, 5.42% (m/v) choline bitartrate, solid-liquid ratio 1:5, 500rpm and pH 7.0 (1.74mgmL−1 theoretical and 1.88mgmL−1 experimental). The kinetic model best fitted to the experimental data was Peleg's, and the best extraction time was 15min. Under optimised conditions, the protein extract of Brazilwood seeds provided a 60.8% inhibition of trypsin. According to the molecular docking results, the inhibition of bovine trypsin is driven by Caesalpinia echinata kallikrein inhibitor (CeKI) and the selected ionic liquid (choline bitartrate), promoting a synergistic inhibition effect.
Unfolding the cascade of SERPINA3: Inflammation to cancer
2022, Biochimica et Biophysica Acta - Reviews on Cancer
SERine Protease INhibitor clade A member 3 (SERPINA3), a member of the SERine-Protease INhibitor (SERPIN) superfamily, principally works as a protease inhibitor in maintaining cellular homeostasis. It is a matricellular acute-phase glycoprotein that appears to be the sole nuclear-binding secretory serpin. Several studies have emerged in recent years demonstrating its link to cancer and disease biology. SERPINA3 seems to have cancer- and compartment-specific biological functions, acting either as a tumour promoter or suppressor in different cancers. However, the localization, mechanism of action and the effectors of SERPINA3 in physiological and pathological scenarios remain obscure. Our review aims to consolidate the current evidence of SERPINA3 in various cancers, highlighting its association with the cancer hallmarks and ratifying its status as an emerging cancer biomarker. The elucidation of SERPINA3-mediated cancer progression and its targeting might shed light on the realm of cancer therapeutics.
The roles of proteases in prostate cancer
2023, IUBMB Life
RECENT BREAKTHROUGHS IN THE MANUFACTURE OF MICROBIAL PROTEASES AND THEIR APPLICATIONS: A REVIEW
2023, International Journal of Pharmaceutical Sciences and Research
A Bioinformatics Assessment Indicating Better Outcomes With Breast Cancer Resident, Immunoglobulin CDR3-MMP2 Binding
2023, Cancer Genomics and Proteomics
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FAQs
What do protease inhibitors do for cancer? ›
A compound that interferes with the ability of certain enzymes to break down proteins. Some protease inhibitors can keep a virus from making copies of itself (for example, AIDS virus protease inhibitors), and some can prevent cancer cells from spreading.
Why are protease inhibitors important? ›Protease inhibitors are medications that help slow the progression of HIV. They do this by blocking the enzyme “protease,” which HIV cells need to develop and mature. Blocking protease prevents the virus from making copies of itself. Protease inhibitors are a type of antiretroviral therapy (ART) medication.
How do you deal with Stage 4 cancer diagnosis? ›If you can, have a consistent daily routine. Make time each day for exercising, getting enough sleep and eating meals. Exercise and participating in activities that you enjoy also may help. People who get exercise during treatment not only deal better with side effects but also may live longer.
What are protease inhibitors mechanisms of action? ›The antiretroviral protease inhibitors act by binding to the catalytic site of the HIV protease, thereby preventing the cleavage of viral polyprotein precursors into mature, functional proteins that are necessary for viral replication.
Which enzyme is used in treatment of cancer? ›Enzyme therapy (more precisely the application of proteases like bromelain, papain or chymotrypsin that are of plant or animal origin) is a method of CAM, which is mainly used to mitigate side-effects of cancer treatment.
What enzyme prevents cancer? ›Researchers found that the enzyme telomerase, which is active in most tumor cells, may also protect healthy adult cells from becoming cancerous. The findings give new insights into cellular aging and the development of cancer.
What are two important functions of the proteases? ›Thus, proteases regulate the fate, localization, and activity of many proteins, modulate protein-protein interactions, create new bioactive molecules, contribute to the processing of cellular information, and generate, transduce, and amplify molecular signals.
What is protease and why is it important? ›Proteases are a powerful tool for modifying the properties of food proteins and producing bioactive peptides from proteins. They are widely used in the production of value-added food ingredients and food processing for improving the functional, nutritional and flavor properties of proteins.
What are the benefits of protease? ›The top protease benefits include its ability to allow for the digestion of proteins and the absorption of amino acids, boost immune function, promote cardiovascular health, accelerate tissue repair and possibly prevent colon cancer.
Why is Stage 4 cancer harder to treat? ›Stage 4 cancer usually can't be cured. In addition, because it's usually spread throughout the body by the time it's diagnosed, it is unlikely the cancer can be completely removed. The goal of treatment is to prolong survival and improve your quality of life.
Why can't metastatic cancer be cured? ›
Rarely are the terms “cure” and “metastatic cancer” used together. That's because cancer that has spread from where it originated in the body to other organs is responsible for most deaths from the disease.
Can 4th stage cancer be treated? ›Stage 4 cancer is challenging to treat, but treatment options may help control the cancer and improve pain, other symptoms and quality of life. Systemic drug treatments, such as targeted therapy or chemotherapy, are common for stage 4 cancers.
What do protease inhibitors block? ›Protease inhibitors (PIs) block protease (an HIV enzyme). By blocking protease, PIs prevent new (immature) HIV from becoming a mature virus that can infect other CD4 cells.
What are the four protease inhibitors? ›Proteases are categorized into four major classes: aspartic proteases, serine proteases, cysteine proteases, and metalloproteases, which contain aspartic acid, serine, cysteine, and metallic ions, respectively, in their active sites.
What are protease inhibitors also known as? ›These drugs are called antiretrovirals because they work against retroviruses such as HIV. Protease inhibitors work to reduce the amount of HIV virus in the blood, also known as viral load. This slows the progression of HIV and helps treat symptoms.
Can enzymes break down cancer cells? ›Scientists have identified a new enzyme mechanism that induces cancer cells that are about to migrate to destroy themselves by degrading their tiny powerhouses, or mitochondria.
What enzymes are involved in cancer metastasis? ›Proteolytic enzymes, such as matrix metalloproteinases, plasminogen activators and cathepsins, as well as non-proteolytic enzymatic partners, such as heparanase and hyaluron-idases, play key roles in the propagation and metastatic potential of cancer cells.
Which enzyme makes cancer cells immortal? ›The currently prevailing immortality theory postulates that cells are immortalized by activation of telomerase. Since this enzyme is developmentally switched off in somatic cells, cancers are said to derive immortality from activation of telomerase.
Which protein controls cancer growth? ›The Myc protein, depicted here, is mutated in more than half of all human cancers. A cancer-associated protein called Myc directly controls the expression of two molecules known to protect tumor cells from the host's immune system, according to a study by researchers at the Stanford University School of Medicine.
What are the 3 main proteases? ›Proteases fall into four main mechanistic classes: serine, cysteine, aspartyl and metalloproteases.
What are 2 examples of protease? ›
| Protease Enzyme Name | Function |
|---|---|
| Pepsin | Present in stomach and converts proteins to smaller peptides – proteoses and peptones |
| Rennin | Secreted by chief cells of the stomach and curdles milk protein |
| Thrombin | Involved in blood coagulation |
| Plasmin | Involved in blood coagulation |
Proteases are released by the pancreas into the proximal small intestine, where they mix with proteins already denatured by gastric secretions and break them down into amino acids, the building blocks of protein, which will eventually be absorbed and used throughout the body.
What would happen without protease? ›Protease. This enzyme breaks down proteins into amino acids. It also helps keep bacteria, yeast, and protozoa out of the intestines. A shortage of protease can lead to allergies or toxicity in the intestines.
What conditions does protease work best in? ›The effect of pH on purified protease activity was determined over a pH range of 3 to 12. The enzyme was found to be highly active in the pH ranges from 7 to 12, with an optimum pH 8 (Figure 2A).
What does protease do in inflammation? ›Proteases are enzymes that have the capacity to hydrolyze peptide bonds and degrade other proteins. Proteases can promote inflammation by regulating expression and activity of different pro-inflammatory cytokines, chemokines and other immune components in the lung compartment.
What enzymes reduce inflammation? ›What enzymes reduce inflammation? Research suggests that bromelain, papain, pancreatin, trypsin, chymotrypsin and rutin all act as essential regulators and modulators of the inflammatory response.
What is the use of protease in daily life? ›- Proteases are in detergent. ...
- Proteases can remove blood stains. ...
- Proteases help make wool. ...
- Protease enzymes recycle silver. ...
- It's a tenderizer. ...
- It has medical therapeutic use.
Immune cells secrete proteases that play roles in the alteration of immune response. Targeting proteases may aid in controlled immunity and decrease the severity of the disease.
How do you stop cancer from metastasis? ›Treatment may include chemotherapy, immunotherapy, targeted therapy, or hormone therapy. Surgery and radiation therapy may also be options for some types of metastatic cancer. Doctors might try one type of treatment and then switch to another when the first treatment no longer works.
What can you do to stop cancer spreading? ›- Don't use tobacco. ...
- Eat a healthy diet. ...
- Maintain a healthy weight and be physically active. ...
- Protect yourself from the sun. ...
- Get vaccinated. ...
- Avoid risky behaviors. ...
- Get regular medical care.
What prevents metastasis? ›
The immune system can effectively prevent the occurrence, development and metastasis of primary tumors through immune surveillance. Immune cells can recognize tumor-specific antigens and destroy cancer cells.
What cancer kills the fastest? ›The Fastest Killing Cancer
If defining "fastest-killing" cancer is based on which cancer has the worst 5-year relative survival rate, then it would be a tie between pancreatic cancer and malignant mesothelioma (a relatively rare cancer in the U.S. with about 3,000 cases a year).
- Chronic lymphocytic leukaemia.
- Chronic myeloid leukaemia.
- Pleural mesothelioma.
- Secondary brain tumours.
- Secondary breast cancer.
- Secondary bone cancer.
- Secondary liver cancer.
- Secondary lung cancer.
Prostate cancer is the easiest cancer to survive, with a 99% 5-year survival rate, provided it is diagnosed in its early stages. Additionally, the 15-year survival rate for prostate cancer is 95%. Doctors regularly screen for prostate cancer, meaning that patients often receive a diagnosis early on.
Can Stage 4 cancer go into remission? ›Thanks to newer cancer treatments, some but not all advanced cancers (Stage IV cancer) may go into partial or complete remission.
When is cancer considered terminal? ›Cancer that cannot be cured and leads to death. Also called end-stage cancer.
Has anyone survived terminal cancer? ›A mother who was given just 12 months to live in 2015 has defied doctors and said she was "stubbornly" clinging on to life.
What is the downside of protease inhibitors? ›Common side effects of protease inhibitors
Nausea and vomiting. Diarrhea. Rash. Cough.
Confirmed potential side effects of protease inhibitors are: Insulin resistance. Nausea and diarrhea. Development of gallstones or kidney stones.
What are the contraindications for protease inhibitors? ›Contraindications. The protease inhibitors are contraindicated in those known to be hypersensitive to them, and should be used cautiously in patients with patients liver disease, hemophilia or diabetes Micromedex (2003).
Is Pfizer a protease inhibitor? ›
The Pfizer compound was developed to inhibit an enzyme called a protease.
What foods are highest in protease inhibitors? ›Protease inhibitors interfere with the action of trypsin and chymostrypsin, enzymes produced by the pancreas to break down ingested proteins. They are found to some extent in cereal grains (oats, barley, and maize), Brussels sprouts, onion, beetroot, wheat, finger millet, and peanuts.
What are the different types of protease inhibitors? ›Protease inhibitors can be further classified into 5 groups (serine, threonine, cysteine, aspartyl and metalloprotease inhibitors) according to the mechanism employed at the active site of proteases they inhibit. Some protease inhibitors interfere with more than one type of protease.
Why use protease inhibitors? ›Protect Your Proteins
Protease inhibitors are valuable and useful reagents for researchers who want to inhibit general degradation of proteins in tissue or cell extracts by endogenous proteases. During isolation and characterization, proteases may pose a threat to the fate of a protein.
Proteases inhibitors are nearly always needed, while phosphatase inhibitors are required only when phosphorylation states (activation states) are being investigated.
What is the role of drug metabolizing enzymes in cancer and cancer therapy? ›Drug-metabolizing enzymes (DME) play a key role in the activation and deactivation of drugs, including a number of cytotoxics (Table 1), and can therefore influence the susceptibility of organs and tissues to their therapeutic and toxic effects.
What are PI3K inhibitors for cancer? ›PI3K inhibitors were designed for those with a PIK3CA gene mutation. Certain cancers, including colorectal, brain, and gastric cancers, have high rates of mutation in this gene; one of the drugs in this class is also an effective treatment for those with breast cancer.
What is an important enzyme involved in cancer development? ›The well-known classic glycolytic enzyme, glyceraldehyde-3-phosphate dehydrogenase (GAPDH; the housekeeping gene) is also implicated in cancer. Overexpression of GAPDH is considered an important feature of numerous types of cancer (28–30).
What are inhibitors for cancer treatment? ›Checkpoint inhibitors are a type of immunotherapy. They are a treatment for cancers such as melanoma skin cancer and lung cancer. These drugs block different checkpoint proteins. You might also hear them named after these checkpoint proteins – for example, CTLA-4 inhibitors, PD-1 inhibitors and PD-L1 inhibitors.
What is the role of PI3K in cancer metabolism? ›Oncogenic activation of the PI3K-AKT pathway in cancer cells reprograms cellular metabolism by augmenting the activity of nutrient transporters and metabolic enzymes, thereby supporting the anabolic demands of aberrantly growing cells.
What is an example of a PI3K inhibitor? ›
There are pan-class I PI3K inhibitors such as copanlisib, isoform-specific PI3K inhibitors such as idelalisib, and dual PI3K/mTOR inhibitors such as dactolisib.