Seasonal variation in the metabolome expression of Jania rubens (Rhodophyta) reveals eicosapentaenoic acid as a potential anticancer metabolite

Abstract Seaweeds of the intertidal zone are subjected to diverse stresses due to environmental changes in radiation, salinity, water quality, herbivore communities, etc. Thus, marine seaweeds developed various unique compounds to deal with environmental fluctuations. Therefore, they are a good source of unique novel compounds. Here, we explored the seasonal metabolomic changes in Jania rubens and found notable changes between extracts of different seasons in the metabolomic profile and in their anticancer activity. The most bioactive extract was from samples collected during the Fall season, which demonstrated an LC50 of 178.39 (± 10.02 SD) µg/ml toward Non Small Cell Lung Cancer (NSCLC) followed by the Winter season extract. The Fall and Winter extracts also displayed more resemblance in their metabolic profile relative to Spring and Summer extracts. The Fall extract was fractionated and tested for cytotoxic activity toward an array of cancer cell lines. Eventually, using a bio-guided assay and multiple fractionation steps, we isolated and identified the essential fatty acid, eicosapentaenoic acid, as the active anticancer agent, showing an LC50 of 5.23 (± 0.07 SD) µg/ml toward NSCLC. Our results emphasize the potential use of J. rubens as a source of beneficial fatty acids and stress the importance of environmental effects on metabolic constitutes