Metabolite profiling of a Sargassum micracanthum methanol extract with in vitro efficacy against human head and neck squamous cell carcinoma aggressiveness

Objective: Extracts from the brown algae Sargassum micracanthum have documented anti-viral, anti-oxidant, and anti-inflammatory activities as well as potential anti-tumor efficacy against several cancer types. Here, we evaluated the inhibitory effect and molecular mechanisms of methanol extract of S. micracanthum (MESM) on the aggressiveness of human head and neck squamous cell carcinoma (HNSCC) using in vitro cell culture-based models.

Design: To test the potential efficacy of MESM on the migratory and invasive properties of HNSCC cells, we used wound healing, transwell cell migration and invasion assays. Proteome profiling and functional in silico analysis were applied to investigate the possible modes of action by MESM. We also examined the metabolite profiling of MESM using gas chromatography/mass spectrometry.

Results: MESM inhibited the motility of human HNSCC cell lines as well as invasiveness without influencing cell survival. Proteome profiling identified 19 oncogenic proteins significantly downregulated by MESM treatment. Protein-protein interaction network and gene ontology analyses revealed that Tie2 and associated angiogenic signaling pathway components were significantly enriched among these downregulated oncogenic proteins, which was confirmed by validating the reduced Tie2 expression in MESM treatment groups. Metabolite profiling of MESM identified six-carbon sugar alcohols such as D-sorbitol and/or D-mannitol as the main bioactive compounds. D-sorbitol and D-mannitol effectively reduced Tie2 expression and the aggressiveness of human HNSCC cell lines.

Conclusions: These findings suggest that six-carbon sugar alcohols in MESM have promising anti-cancer efficacy for the treatment of human HNSCC and further identify Tie2 signaling components as potential treatment targets.