Search Results (2)

In the soft treatment of cancer tumours, consequent downregulation of the malignant tissue angiogenesis constitutes an efficient way to stifle tumour development and metastasis spreading. As angiogenesis requires integrin–promoting endothelial cell adhesion, migration, and vessel tube formation, integrins represent potential targets of new therapeutic anti–angiogenic agents. Our work is a contribution to the research of such therapeutic disintegrins in animal venoms. We report isolation of one peptide, named Dabmaurin–1, from the hemotoxic venom of snake Daboia mauritanica, and we evaluate its potential anti–tumour activity through in vitro inhibition of the human vascular endothelial cell HMECs functions involved in tumour angiogenesis. Dabmaurin–1 altered, in a dose–dependent manner, without any significant cytotoxicity, HMEC proliferation, adhesion, and their mesenchymal migration onto various extracellular matrix proteins, as well as formation of capillary–tube mimics on Matrigel^TM. Via experiments involving HMEC or specific cancers cells integrins, we demonstrated that the above Dabmaurin–1 effects are possibly due to some anti–integrin properties. Dabmaurin–1 was demonstrated to recognize a broad panel of prooncogenic integrins (αvβ6, αvβ3 or αvβ5) and/or particularly involved in control of angiogenesis (α5β1, α6β4, αvβ3 or αvβ5). Furthermore, mass spectrometry and partial N–terminal sequencing of this peptide revealed, it is close to Lebein–1, a known anti–β1 disintegrin from Macrovipera lebetina venom. Therefore, our results show that if Dabmaurin–1 exhibits in vitro apparent anti–angiogenic effects at concentrations lower than 30 nM, it is likely because it acts as an anti–tumour disintegrin. Full article

Melanoma, the most threatening form of skin cancer, has a very poor prognosis and is characterized by its very invasive and chemoresistant properties. Despite the recent promising news from the field of immunotherapy, there is an urgent need for new therapeutic approaches that are free of resistance mechanisms and side effects. Anti-neoplasic properties have been highlighted for different disintegrins from snake venom including Lebein; however, the exact effect of Lebein on melanoma has not yet been defined. In this study, we showed that Lebein blocks melanoma cell proliferation and induces a more differentiated phenotype with inhibition of extracellular signal-regulated kinase (ERK) phosphorylation and microphthalmia-associated transcription factor (MITF) overexpression. Melanoma cells became detached but were less invasive with upregulation of E-cadherin after Lebein exposure. Lebein induced a caspase-independent apoptotic program with apoptosis inducing factor (AIF), BCL-2-associated X protein (BAX) and Bim overexpression together with downregulation of B-cell lymphoma-2 (BCL-2). It generated a distinct response in reactive oxygen species (ROS) generation and p53 levels depending on the p53 cell line status (wild type or mutant). Therefore, we propose Lebein as a new candidate for development of potential therapies for melanoma. Full article