Exploring the potential of Arbacia lixula coelomic fluid peptides as cell cycle and angiogenesis inhibitor for triple-negative breast cancer therapy: In silico study

Context: Triple-negative breast cancer (TNBC) is a breast malignancy with a high degree of heterogeneity. Currently, low treatment efficacy remains a challenge in dealing with TNBC. Arbacia lixula has the potential to become a new therapeutic agent in TNBC. Aims: To analyze the toxicity, allergenicity, and potential of A. lixula coelomic fluid peptides as agents that inhibit cell cycle progression and angiogenesis in TNBC cancer cells in silico. Methods: Eight A. lixula coelomic fluid peptides were modeled with UCSF Chimera software. All peptides were screened using the ToxinPred and AllerTop webserver to predict their toxicity and allergenicity. The 3D structures of GSK3B, CDK2, and VEGFR2 proteins were taken from the PDBJ database. Molecular docking was carried out using the MOE application. Results: Peptides 2, 4, 6, and 7 were non-toxic and non-allergen. Peptide 4 has the strongest binding affinity value for binding the ATP binding pocket proteins GSK3β (-11.57 kcal/mol) and VEGFR2 (-11.18 kcal/mol). Peptide 4 interacts similarly with ATP, as a native ligand, on the amino acid residues of GSK3B and VEGFR2. Peptide 1 has a binding affinity value of -10.16 kcal/mol, much stronger than ATP in the CDK2 protein, and forms the same two interactions as ATP at the amino acid residues Asp86 and Lys129. Conclusions: Peptide 1 and peptide 4 of A. lixula coelomic fluid have great potential as anti-TNBC by inhibiting the activity of proteins that play a crucial role in cell cycle progression and TNBC angiogenesis via an ATP competitive inhibitor mechanism through an in silico approach.