Tailor-made Biochar enhances the anti-tumour effects of butyrate-glycerides in colorectal cancer

Colorectal cancer (CRC) is the third most common cancer and the second cause of cancer death in the world. Emerging evidence suggests that the short-chain-fatty-acid butyrate diet-assumed or produced by gut microbiota may interfere with CRC. Novel, more focused and effective anti-cancer natural molecules selectively acting on tumour cells are required to improve patients' compliance compared to more aggressive drug-based schemes. This study explored the in vitro anti-cancer effects of a novel green compound consisting of butyrate-glycerides (BMDG) alone or absorbed on tailor-made Biochar (BMDG-Biochar) or on activated-carbon Norit-B (BMDG-Norit), by using two CRC cell lines, HCT116 and HT29. Tailor-made Biochar characterised by a larger share of meso and macroporosity compared to commercially available activated-carbon Norit-B, with micro-pored ultrastructure, displayed superior performances as a BMDG carrier, with higher absorption/release properties. BMDG, in particular when absorbed on Biochar, interfered significantly with CRC cell proliferation compared to BMDG-Norit that showed no effect. Analysis of cell metabolism revealed a superior sensitivity of HCT116 to the inhibitory effect of BMDG-Biochar. This compound specifically induced a shift from a glycolytic metabolism in particular in HCT116 cells where glycolysis supports the aggressive phenotype, towards the mitochondrial respiration that characterises the more differentiated and less aggressive HT29 cells. Biochar's ability to deliver the butyrate-glyceride bioactive mixture and to exert in vitro combined anti-cancer activity in colorectal cancer, interfering with the Warburg effect that characterises the aggressive CRC forms, opens future translational opportunities to develop new orally assumed green molecules as promising anti-cancer strategies for CRC.