Scytonemin extracted from <i>Lyngbya aestuarii</i> exhibits anti-cancer activity: involvement of c-Myc pathway inhibition

The increasing incidence of cancer-related morbidity and mortality underscores the urgent need for novel, less toxic therapeutic options. In this study, we isolated scytonemin from the marine cyanobacterium <i>Lyngbya aestuarii</i>. Its identification was confirmed through an absorption peak at 384 nm and MALDI-TOF MS analysis showing a [M + H]⁺ ion at m/z 545.838, consistent with its oxidised form (C₃₆H₂₀N₂O₄). Scytonemin demonstrated significant cytotoxicity against breast cancer cell lines MDA-MB-231 and MCF-7, with IC₅₀ values of 8 μM and 4 μM, respectively, while remaining non-toxic to human peripheral blood lymphocytes (HPBLs). The compound rapidly induced caspase-dependent intrinsic apoptosis within 2 h, with apoptotic effects magnifying at 24 and 48 h. Molecular docking and reporter gene assays revealed that scytonemin inhibits two critical proteins associated with cancer progression c-Myc and Polo-like kinase 1 (PLK1). These results suggest that scytonemin holds promise as a lead compound for the development of targeted anti-cancer therapies.