Moojecin: The first disintegrin from Bothrops moojeni venom and its antitumor activity in acute myeloid leukemia

• Published in: International journal of biological macromolecules 2024-11, Vol.279 (Pt 1), p.135066, Article 135066
• Main Authors: Almeida, Gabriela de Oliveira, Cintra, Adélia Cristina Oliveira, Silva, Thiago Abrahão, de Oliveira, Isadora Sousa, Correia, Lucas Ian Veloso, Torquato, Ricardo José Soares, Ferreira Junior, Rui Seabra, Arantes, Eliane Candiani, Sampaio, Suely Vilela
• Format: Article
• Language: English
• Subjects: Acute myeloid leukemia; angiogenesis; Animals; antineoplastic activity; Antineoplastic Agents - chemistry; Antineoplastic Agents - isolation & purification; Antineoplastic Agents - pharmacology; Bothrops; cell adhesion; Cell Line, Tumor; Cell Movement - drug effects; Cell Proliferation - drug effects; chromatography; class; Crotalid Venoms - chemistry; cytotoxicity; Disintegrins; Disintegrins - chemistry; Disintegrins - isolation & purification; Disintegrins - pharmacology; dose response; hemolysis; HL-60 Cells; Humans; integrins; Leukemia, Myeloid, Acute - drug therapy; molecular weight; myeloid leukemia; neoplasm progression; peptides; platelet aggregation; Platelet Aggregation - drug effects; Snake venom; snake venoms; Venomous Snakes
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.135066

Disintegrins are a class of peptides found in snake venom that inhibit the activity of integrins, which are essential cell adhesion receptors in tumor progression and development. In this work, moojecin, a RGD disintegrin, was isolated from Bothrops moojeni snake venom, and its antitumor potential in acute myeloid leukemia (AML) HL-60 and THP-1 cells was characterized. The isolation was performed using a C18 reverse-phase column in two chromatographic steps, and its molecular mass is 7417.84 Da. N-terminal and de novo sequencing was performed to identify moojecin. Moojecin did not show cytotoxic or antiproliferative activity in THP-1 and HL-60 at tested concentrations, but it exhibited significant antimigratory activity in both cell lines, as well as inhibition of angiogenesis in the tube formation assay on Matrigel in a dose-dependent manner. A stronger interaction with integrin αVβ3 was shown in integrin interaction assays compared to α5β1, and the platelet aggregation assay indicated an IC50 of 5.039 μg/mL. Preliminary evaluation of disintegrin toxicity revealed no incidence of hemolysis or cytotoxic effects on peripheral blood mononuclear cells (PBMCs) across the tested concentrations. Thus, this is the first study to report the isolation, functional and structural characterization of a disintegrin from B. moojeni venom and bring a new perspective to assist in AML treatment. [Display omitted] •Isolation and characterization of moojecin, a disintegrin from Bothrops moojeni venom•Moojecin inhibits migration and invasion of acute myeloid leukemia cells without cytotoxic effects.•Moojecin inhibits angiogenesis and has antitumor activity against HL-60 and THP-1 cells.•Moojecin, like other snake venom disintegrins, may present potential for novel cancer treatments.