In vitro and in silico analysis of the anti-proliferative effects of Spirulina platensis on A549 lung cancer cells.
Fatma I Abo El-Ela, Marwa A Ibrahim, Salma I El-Samannoudy, Walid Hamdy Hassan, Doaa R I Abdel-Gawad
Abstract
Open AccessSpirulina platensis (S. platensis) is a natural microalgae extract that exerts significant cytotoxic effects against different serious cancerous diseases. Lung cancer is one of the most common and leading causes of death all over the world. The purpose is to investigate the anti-proliferative cytotoxic effects of S. Platensis against the adenocarcinomic human alveolar basal epithelial cells (A549 cell line). Also, molecular docking Analysis and pathway Map were investigated. The viability of the cells was determined via the MTT assay. Moreover the lipid peroxidation, total thiol, the protein concentration of Microtubule-associated tumor suppressor 1 (MTUS1), P16, Kirsten rat sarcoma viral oncogene homolog (K-ras), the epidermal growth factor receptor (EGFr), and the molecular parameters (short stature homeobox 2 (SHOX2), Breast cancer metastasis suppressor 1 (BRMS1), B-cell lymphoma 2 (BCL-2), and Bcl-2-associated X protein (BAX) were assessed. In order to define interaction sites and classes, the current study investigates in detail the interactions between the ligand S. platensis and the Interleukin enhancer-binding factor 3 Receptor (IL-F3) of lung cancer. Covalent bonds, H-bonds, and hydrophobic interactions were observed to form with critical residues on the active site. Covalent bonds are identified in seventeen of the complexes. A correlation was observed between binding affinity and molecular size, branching, polar surface area of up to 199 Å2, hydrophilicity, and topological diameter for various bonds. In an effort to enhance pharmaceutical quality control, we utilized in silico methodologies to forecast the ADMET (absorption, distribution, metabolism, excretion, and toxicity) of S. platensis. Results revealed a great anti-proliferative cytotoxic effect with a concentration gradient through decreasing the peroxidation content, and the epigenetic markers, with significant up-regulations of the BRMS1 and BAX. In addition to the kinetic and MAP pathways, docking analysis confirmed that S. platensis binds with the highest affinity to the predicted active sites of the tumor receptor IL-F3, thereby validating its antitumor activity. In conclusion, great suppression in the virulence of lung cancer was reported following treatment with S. platensis, illustrating its suspected mechanism of action, safety profile, kinetic properties, molecular docking results, toxicity, and internal pathways.