Rare sugar l-sorbose exerts antitumor activity by impairing glucose metabolism

The rare sugar L-sorbose is shown to decrease cell viability and increase apoptotic cells in culture and to enhance the effect of tumor chemotherapy in combination with sorafenib in mouse xenograft models. Rare sugars are monosaccharides with low natural abundance. They are structural isomers of dietary sugars, but hardly be metabolized. Here, we report that rare sugar l-sorbose induces apoptosis in various cancer cells. As a C-3 epimer of d-fructose, l-sorbose is internalized via the transporter GLUT5 and phosphorylated by ketohexokinase (KHK) to produce l-sorbose-1-phosphate (S-1-P). Cellular S-1-P inactivates the glycolytic enzyme hexokinase resulting in attenuated glycolysis. Consequently, mitochondrial function is impaired and reactive oxygen species are produced. Moreover, l-sorbose downregulates the transcription of KHK-A, a splicing variant of KHK. Since KHK-A is a positive inducer of antioxidation genes, the antioxidant defense mechanism in cancer cells can be attenuated by l-sorbose-treatment. Thus, l-sorbose performs multiple anticancer activities to induce cell apoptosis. In mouse xenograft models, l-sorbose enhances the effect of tumor chemotherapy in combination with other anticancer drugs. These results demonstrate l-sorbose as an attractive therapeutic reagent for cancer treatment.

Automated summary

The rare sugar L-sorbose has been found to decrease cell viability and increase apoptotic cells in culture, and it enhances the effect of tumor chemotherapy in mouse xenograft models. It acts as a C-3 epimer of d-fructose, and it induces apoptosis by inactivating glycolytic enzyme and impairing mitochondrial function, while also downregulating the transcription of KHK-A, which attenuates the antioxidant defense mechanism in cancer cells.