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op den Brouw, Bianca, Ghezellou, Parviz, Casewell, Nicholas 
ORCID: https://orcid.org/0000-0002-8035-4719, Ali, Syed Abid, Fathinia, Behzad, Fry, Bryan G., Bos, Mettine H.A. and Ikonomopoulou, Maria P.
(2021)
'Pharmacological Characterisation of Pseudocerastes and Eristicophis Viper Venoms Reveal Anticancer (Melanoma) Properties and a Potentially Novel Mode of Fibrinogenolysis'. International Journal of Molecular Sciences, Vol 22, Issue 13, p. 6896.
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Abstract
Venoms are a rich source of potential lead compounds for drug discovery, and descriptive studies of venom form the first phase of the biodiscovery process. In this study, we investigated the
pharmacological potential of crude Pseudocerastes and Eristicophis snake venoms in haematological isorders and cancer treatment. We assessed their antithrombotic potential using fibrinogen thromboelastography, fibrinogen gels with and without protease inhibitors, and colourimetric fibrinolysis assays. These assays indicated that the anticoagulant properties of the venoms are likely induced by the hydrolysis of phospholipids and by selective fibrinogenolysis. Furthermore, while most fibrinogenolysis occurred by the direct activity of snake venom metalloproteases and serine proteases, modest evidence indicated that fibrinogenolytic activity may also be mediated by selective venom phospholipases and an inhibitory venom-derived serine protease. We also found that the Pseudocerastes venoms significantly reduced the viability of human melanoma (MM96L) cells by more than 80%, while it had almost no effect on the healthy neonatal foreskin fibroblasts (NFF) as determined by viability assays. The bioactive properties of these venoms suggest that they contain a number of toxins suitable for downstream pharmacological development as candidates for antithrombotic or anticancer agents.
| Item Type: | Article |
|---|---|
| Subjects: | QV Pharmacology > Anti-Inflammatory Agents. Anti-Infective Agents. Antineoplastic Agents > QV 269 Antineoplastic agents. Antineoplastic antibiotics WD Disorders of Systemic, Metabolic or Environmental Origin, etc > Animal Poisons > WD 410 Reptiles WH Hemic and Lymphatic Systems > Hematologic Diseases. Immunologic Factors. Blood Banks > WH 140 Hematopoietic system and hematopoiesis. Developmental theories. Blood cells (General) |
| Faculty: Department: | Biological Sciences > Department of Tropical Disease Biology |
| Digital Object Identifer (DOI): | https://doi.org/10.3390/ijms22136896 |
| Depositing User: | Cathy Waldron |
| Date Deposited: | 13 Sep 2021 11:29 |
| Last Modified: | 13 Sep 2021 11:29 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/18910 |
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