Fructose slows liver tumors in mice when key sugar-processing gene is missing, may lead to new treatments

Researchers at City University of Hong Kong have discovered that fructose can suppress liver tumors in mice when the enzyme responsible for breaking down fructose is missing. This finding, published in Signal Transduction and Targeted Therapy, suggests a new potential treatment for hepatocellular carcinoma (HCC), one of the leading causes of cancer deaths worldwide.

When researchers created a mouse model of HCC with a knockout of the gene ALDOB, which breaks down fructose, they found that feeding these mice fructose significantly reduced tumor growth. This is because ALDOB deficiency leads to an accumulation of fructose 1-phosphate (F1P), which inhibits mannose phosphate isomerase (MPI). Disrupting MPI interferes with protein glycosylation, triggering endoplasmic reticulum stress and inducing cancer cell apoptosis.

The researchers also identified mannose as a bypassing agent that can reverse the anticancer effect of fructose, confirming MPI as the key node in this pathway. Additionally, they discovered that the FDA-approved drug ebselen, which inhibits MPI, suppresses liver cancer growth in mouse models and enhances the effectiveness of sorafenib, an existing liver cancer therapy. Ebselen's safety profile makes it a promising candidate for clinical translation.

This research challenges the conventional view that fructose is universally detrimental to health, demonstrating its potential benefits in specific disease contexts. The findings could lead to new metabolic therapies for liver cancer, a disease with limited treatment options.