Brown seaweed extracts inhibit glycolysis and metastasis of cancer cells

Metastasis is promoted by metabolic reprogramming (increased glycolysis and decreased mitochondrial respiration) and the expression of Caveolin-1 (CAV1). Bioactive compounds, such as phloroglucinol, prevent glycolysis and metastasis. Brown seaweeds are consumed as dietary supplements due to their nutritional and antihyperglycemic benefits. Chilean brown seaweed ( Durvillaea incurvata ) contains phlorotannins, which are polymers of phloroglucinol. Here, we sought to investigate the anti-glycolytic and anti-metastatic potential of extracts from Durvillaea incurvata in metastatic cancer cell lines (MDA-MB-231 and B16-F10), which either express or not CAV1. These extracts prevented migration in vitro and metastasis in vivo . Moreover, in cells treated with the extracts, a significant reduction in glycolysis was observed, which was linked to the inhibition of hexokinase activity. Additionally, the extract contains carmalol and eckol (C 18 H 12 O 12 and C 48 H 30 O 21 , respectively), identified as the most abundant phlorotannins, and also potential inhibitors of hexokinase-2, demonstrated by molecular docking analysis. However, the extracts might contain other bioactive compounds with potential anti-tumoral effects that need to be analyzed in the future. These findings suggest that brown seaweed extracts may represent a readily available, cheap, and sustainable source of bioactive compounds with potential anti-metastatic activity, highlighting the relevance of these natural products as potential cancer therapeutics.