Marine-Derived Chemotherapeutic Agent for Acute Leukemia: In Silico and In Vitro Evaluation

Acute leukemia, a severe hematological malignancy marked by abnormal white blood cell proliferation, often resists conventional therapies. The growing interest in natural therapeutics has spotlighted marine-derived compounds for their unique bioactivities. This study explores the therapeutic potential of Ascophyllum nodosum extract, focusing on Laminine, in modulating key leukemia-associated proteins, lactate dehydrogenase (LDH), and phosphoinositide 3-kinase (PIK3), using in silico and in vitro approaches. Molecular docking was performed to assess Laminine's binding interactions with LDH and PIK3. An in vitro leukemia model was adopted using N-Nitroso-N-ethylurea-treated Wistar rats. Efficacy was evaluated through LDH release, PIK3 activity, hematological parameters, and clinical signs of leukemia. Docking studies revealed moderate binding affinities (-6.5 kcal/mol) of Laminine with LDH and PIK3, suggesting potential therapeutic interactions. In vitro, the extract demonstrated dose-dependent cytoprotective effects, reducing LDH release and restoring PIK3 activity. Leukemia-induced hematological abnormalities, including elevated white blood cell counts, anemia, and thrombocytopenia, were partially reversed. The highest dose (50 µM) showed maximal efficacy in reducing cytotoxicity and modulating signaling pathways. A. nodosum extract, particularly Laminine, shows potential as a therapeutic candidate against leukemia by targeting metabolic and signaling pathways. Further research is needed to optimize its clinical utility and elucidate its mechanisms.