Disintegrins from the Venom of Vipera ammodytes ammodytes Efficiently Inhibit Migration of Breast Cancer Cells

Abstract

Integrins are plasma membrane proteins, whose dysfunction frequently results in cancer pathology, and therefore they represent important targets of anti-tumour therapy. Snake venoms are a rich source of disintegrins (Dis), proteins that specifically bind integrins and thus interfere with their functions. In an attempt to discover new molecules for treatment of breast cancer, the major type of cancer in women, we isolated a dimeric Dis (Vaa-Dis) from the venom of the nosehorned viper. By cell viability testing we demonstrated that 50 nM and higher concentrations of Vaa-Dis were toxic to highly invasive human breast adenocarcinoma cell line MDA-MB-231. Wound-healing assay revealed that already at one order of magnitude lower concentrations Vaa-Dis efficiently inhibited MDA-MB-231 cell migration. This exposed a promising anti-metastatic potential of Vaa-Dis and a good perspective of these natural snake venom proteins for further research and development towards the application in breast cancer treatment.

Comprehensive Study of the Proteome and Transcriptome of the Venom of the Most Venomous European Viper: Discovery of a New Subclass of Ancestral Snake Venom Metalloproteinase Precursor-Derived Proteins

“…Disintegrins comprise another family of nonenzymatic dimeric toxins present in the Vaa venom (Tables and ; Table S-2). ,, They are common constituents of Viperinae venoms that act as integrin antagonists. − β-Subunits of dimeric Dis are derived from P-II SVMP precursors (e.g., Vaa-MPII-1, Vaa-MPII-2, and Vaa-MPII-3) in the process of post-translational proteolytic processing. α-Subunits, for example, Vaa-Dis-1, Vaa-Dis-2, and VA6, are encoded per se, by short-coding mRNAs that do not include a message for the MP domain .…”

“…As expected, a mixture of Vaa Dis significantly slowed down the migration of cancer cells. 15 3.2.1.9. Cys-Rich Secretory Proteins.…”

“…11 The Vbb proteome was shown to be much less complex than that of Vaa , in particular, possessing smaller amounts of snaclecs (snake C-type lectin-like proteins) and sPLA 2 s. The Vaa venom is rich in compounds that interfere with hemostasis, 12,13 with some that are potentially anti-tumor-active. 14,15…”

“…11 The Vbb proteome was shown to be much less complex than that of Vaa, in particular, possessing smaller amounts of snaclecs (snake C-type lectinlike proteins) and sPLA 2 s. The Vaa venom is rich in compounds that interfere with hemostasis, 12,13 with some that are potentially anti-tumor-active. 14,15 The main aim of the present comprehensive transcriptomic and proteomic study was to identify and build a complete library of Vaa venom proteins and peptides. The accumulated data will direct the production of a more specific and effective antivenom with which to treat venomous Vaa bites.…”

“…Recently, we studied the proteome of the common European adder, subspecies Vipera berus berus ( Vbb ), and compared it with that of Vaa . The Vbb proteome was shown to be much less complex than that of Vaa , in particular, possessing smaller amounts of snaclecs (snake C-type lectin-like proteins) and sPLA 2 s. The Vaa venom is rich in compounds that interfere with hemostasis, , with some that are potentially anti-tumor-active. , …”