Marine cyanobacteria offer a rich source of varied natural products with both chemical and biological diversity. Oscillatoria salina (O. salina) is a filamentous non-heterocystous marine cyanobacterium from Oscillatoriaceae family. In this investigation, we have unveiled bioactive extracts from O. salina using two distinct solvent systems, revealing significant anticancer properties. Our assessment of the organic and aqueous extracts (MCE and AE) of O. salina demonstrated pronounced antiproliferative and antimetastatic effects. Notably, this study is the first to elucidate the anticancer and anti-metastatic potential of O. salina extracts in both 2D and 3D cell culture models. Both MCE and AE induced apoptosis, hindered cell proliferation, invasion, and migration in A549 non-small cell lung cancer cells, accompanied by alterations in cell morphology and cytoskeleton collapse. Moreover, MCE and AE induced spheroid disintegration in A549 cells. Transcriptomics analysis highlighted the significant involvement of Rap1 and p53 signaling pathways in mediating the observed antitumor effects. Mass spectroscopy characterization of these extracts identified 11 compounds, some known for their anticancer potential. HPLC analysis of AE revealed six peaks with UV absorption spectra resembling phycocyanin, a cyanobacterial pigment with well-known anticancer activity. Collectively, these findings underscore the anticancer potential of MCE and AE, containing bioactive metabolites with anticancer and antimetastatic properties.
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