Targeting Metastasis with Snake Toxins: Molecular Mechanisms

Urra, Félix A.; Araya‐Maturana, Ramiro

doi:10.3390/toxins9120390

Cited by 26 publications

(22 citation statements)

References 97 publications

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“…While replacement of Met 28 with Asn completely abolished its ability to recognize integrin [ 131 ]. Recently, Urra and Araya-Maturana reviewed the anti-metastatic mechanism of snake venom toxins in detail and summarized that snake venom toxins (particularly snake venom cystatins, disintegrins, lectins, and cardiotoxins) inhibit pro-migratory and pro-invasive signals stimulated by extracellular matrix proteins and growth factors [ 29 ].…”

Section: Snake Venom Peptides and Their Potential Pharmacological mentioning

confidence: 99%

Snake Venom Peptides: Tools of Biodiscovery

Munawar

Ali

Akrem

et al. 2018

Toxins

113

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Nature endowed snakes with a lethal secretion known as venom, which has been fine-tuned over millions of years of evolution. Snakes utilize venom to subdue their prey and to survive in their natural habitat. Venom is known to be a very poisonous mixture, consisting of a variety of molecules, such as carbohydrates, nucleosides, amino acids, lipids, proteins and peptides. Proteins and peptides are the major constituents of the dry weight of snake venoms and are of main interest for scientific investigations as well as for various pharmacological applications. Snake venoms contain enzymatic and non-enzymatic proteins and peptides, which are grouped into different families based on their structure and function. Members of a single family display significant similarities in their primary, secondary and tertiary structures, but in many cases have distinct pharmacological functions and different bioactivities. The functional specificity of peptides belonging to the same family can be attributed to subtle variations in their amino acid sequences. Currently, complementary tools and techniques are utilized to isolate and characterize the peptides, and study their potential applications as molecular probes, and possible templates for drug discovery and design investigations.

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Section: Snake Venom Peptides and Their Potential Pharmacological mentioning

confidence: 99%

Snake Venom Peptides: Tools of Biodiscovery

Munawar

Ali

Akrem

et al. 2018

Toxins

113

View full text Add to dashboard Cite

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“…which cause loss of the cell process viability; and (iii) Viperidae venoms ( Macrovipera spp. ), which cause alterations of cell aggregation [ 85 , 86 ].…”

Section: Zootherapymentioning

confidence: 99%

Zoopharmacology: A Way to Discover New Cancer Treatments

et al. 2020

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Zoopharmacognosy is the multidisciplinary approach of the self-medication behavior of many kinds of animals. Recent studies showed the presence of antitumoral secondary metabolites in some of the plants employed by animals and their use for the same therapeutic purposes in humans. Other related and sometimes confused term is Zootherapy, which consists on the employment of animal parts and/or their by-products such as toxins, venoms, etc., to treat different human ailments. Therefore, the aim of this work is to provide a brief insight for the use of Zoopharmacology (comprising Zoopharmacognosy and Zootherapy) as new paths to discover drugs studying animal behavior and/or using compounds derived from animals. This work is focused on the approaches related to cancer, in order to propose a new promising line of research to overcome multidrug resistance (MDR). This novel subject will encourage the use of new alternative prospective ways to find new medicines.

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“…SVMPs have been studied for several therapeutic purposes. Since they interact with cell membrane components, these enzymes have been shown to inhibit angiogenesis, cell migration and adhesion, which are important mechanisms in cancer proliferation and makes these enzymes important tools in metastatic tumours treatment [ 17 – 20 ]. Metalloproteases also can act as therapeutic tools in arthritis disorders [ 21 , 22 ] and in haemostatic diseases [ 23 ].…”

Section: Introductionmentioning

confidence: 99%

Purification and enzymatic characterization of a novel metalloprotease from Lachesis muta rhombeata snake venom

Cordeiro

Coutinho

Wiezel

et al. 2018

J Venom Anim Toxins Incl Trop Dis

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BackgroundLachesis muta rhombeata (Lmr) is the largest venomous snake in Latin America and its venom contains mainly enzymatic components, such as serine and metalloproteases, L-amino acid oxidase and phospholipases A2. Metalloproteases comprise a large group of zinc-dependent proteases that cleave basement membrane components such as fibronectin, laminin and collagen type IV. These enzymes are responsible for local and systemic changes, including haemorrhage, myonecrosis and inflammation. This study aimed the isolation and enzymatic characterization of the first metalloprotease (Lmr-MP) from Lmr venom (LmrV).Methods and resultsLmr-MP was purified through two chromatographic steps and submitted to enzymatic characterization. It showed proteolytic activity on azocasein with maximum activity at pH 7.0–9.0. It was inhibited by EDTA (a metal chelator that removes zinc, which is essential for enzymatic activity) and no effect was observed with PMSF, iodoacetic acid or pepstatin (inhibitors of serine, cysteine and aspartyl proteases, respectively). Ca2+, Mg2+ and Ba2+ ions increased its activity, while Al3+, Cu2+, Ni2+ and Zn2+ inhibited it. Additionally, ZnCl2 showed a dose dependent inhibition of the enzyme. Lmr-MP activity was also evaluated upon chromogenic substrates for plasma kallikrein (S-2302), plasmin and streptokinase-activated plasminogen (S-2251) and Factor Xa (S-2222) showing the highest activity on S-2302. The activity in different solutions (5 mM or 50 mM ammonium bicarbonate, pH 7.8; 0.1% trifluoroacetic acid + 50% acetonitrile; phosphate buffer saline, pH 7.4; 50 mM sodium acetate, pH 4.0 or ammonium acetate pH 4.5) was also evaluated and the results showed that its activity was abolished at acidic pHs. Its molecular mass (22,858 Da) was determined by MALDI-TOF and about 90% of its primary structure was verified by high-resolution mass spectrometry using HCD and ETD fragmentations and database search against the sequence of closely related species. It is a novel enzyme which shared high identity with other snake venom metalloproteases (svMPs) belonging to the P-I group.ConclusionThe purification procedure achieved a novel pure highly active metalloprotease from LmrV. This new molecule can help to understand the metalloproteases mechanisms of action, the Lachesis envenoming, as well as to open new perspectives for its use as therapeutic tools.

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Targeting Metastasis with Snake Toxins: Molecular Mechanisms

Cited by 26 publications

References 97 publications

Snake Venom Peptides: Tools of Biodiscovery

Snake Venom Peptides: Tools of Biodiscovery

Zoopharmacology: A Way to Discover New Cancer Treatments

Purification and enzymatic characterization of a novel metalloprotease from Lachesis muta rhombeata snake venom

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