NEW INNOVATIVE ANTI-CANCER APPROACHES: THE POTENTIAL OF BUTYRATE-GLYCERIDES IN COLORECTAL CANCER AND THE INTERACTION OF THE ADIPOSE MICROENVIRONMENT IN HEPATOCELLULAR CARCINOMA

This PhD research work 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 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 BMDG 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. During the six months I spent at the Faculty of Biology at the University of Barcelona for my PhD, I also worked on standardizing a co-culture system to investigate the in vitro cross-talk between differentiated and undifferentiated brown adipose cells and hepatocellular carcinoma, focusing on the effects on a hepatocellular carcinoma cell line (HepG2) isolated from a HCC of a 15-year-old, white, male youth with liver cancer, in terms of cell health, proliferation rate and invasiveness. Our results suggest that undifferentiated adipocytes represent pivotal components of the tumor microenvironment, with a central role in mediating HCC invasive reprogramming, by establishing a dynamic crosstalk with cancer cells and promoting tumor progression. When, on the other hand, the tumour cell is co-cultured with differentiated adipocytes, no true crosstalk appears to be established.