Hepatocellular carcinoma, aka liver cancer, is an ever-increasing issue in the western world. While the lion’s share of cases are related to alcohol consumption, non-alcoholic liver disease dependent liver cancer is rising.
Western diets differ from many other parts of the world. We often eat in excess, and in particular, consume large quantities of sugar. Fructose is one such sugar, and several studies have linked it to an increase in hepatocellular carcinoma incidence. In a new study, a team from the Australian Institute of Tropical Health and Medicine sought to examine how fructose affected hepatocellular carcinoma both in vitro and in vivo.
The team’s hypothesis stemmed from the theory that fructose-dependent hepatocellular carcinoma incidence might be related to the pentose phosphate and serine to glycine synthesis pathways. The pentose phosphate pathway generates critical molecules for several systems (nucleotide precursors, NADPH, and other pentose sugars). The serine to glycine synthesis pathway is similar in that it produces essential precursors, and both pathways run alongside the energy-producing system glycolysis, which many cancers use for energy. This leads some scientists to believe its overactivation could enhance glycolysis and support faster cancer growth.
This study focused on examining how fructose affected the growth of hepatocellular carcinoma cells in vitro and in vivo. The team also tested the pentose phosphate pathway inhibitor Physcion and the serine to glycine synthesis pathway inhibitor NCT-503 to determine if either could produce anti-cancer effects.
Initial testing showed that hepatocellular carcinoma cells and tumors actually grew slower in the presence of excess fructose. Later analysis showed that fructose increased apoptosis. Inhibiting the serine to glycine synthesis pathway with NCT-503 impaired cancer growth in the presence of fructose, with the combination treatment showing slightly better results. Inhibiting the pentose phosphate pathway with Physcion showed only weak effects.
This study shows that fructose seems to inhibit the growth of hepatocellular carcinoma rather than promote it. NCT-503 also managed to suppress the growth of hepatocellular carcinoma both in vitro and in vivo, with Physcion showing little to no impact. These results contradict other studies, although the team could not explain why.
The study concludes, “In conclusion, this study is the first to utilise a high fructose diet as means to manipulate the metabolic environment of HCC tumour growth.”
Sources: Nature Scientific Reports, UT Health Science Center at Tyler