Brown seaweed extracts inhibit glycolysis and metastasis of cancer cells

Abstract

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 (C18H12O12 and C48H30O21, 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.