What is the anti-cancer mechanism of Mannose?

News

What is the anti-cancer mechanism of Mannose?

In mammals, Mannose (Mannose) , a monosaccharide essential to life, is de novo synthesized from glucose through a branched pathway of glycolysis.

Mannose is a natural sugar that is abundant in many fruits and vegetables . Some recent studies have shown that Mannose can effectively promote immune tolerance, suppress inflammatory diseases, and effectively suppress tumors by inhibiting glycolysis . However, it is not entirely clear how Mannose exerts its anticancer effects.

On July 18, 2023, researchers from the International Cancer Institute in Osaka, Japan published a research paper entitled: Metabolic clogging of Mannose triggers dNTP loss and genomic instability in human cancer cells in the journal eLife .

The study sheds light on the anticancer mechanism of Mannose and suggests that Mannose may be a promising therapeutic for cancer replication.

What is the anti-cancer mechanism of Mannose?

Mannose has anticancer activity, can inhibit cell proliferation, and improve the effect of chemotherapy. However, exactly how Mannose exerts its anticancer activity remains poorly understood .

Mannose has been known to be deadly to bees for more than 100 years because bees cannot process Mannose the way humans do, leading to the fatal bee syndrome. So is there a link between bee syndrome and the cancer-fighting properties of Mannose ?

Researchers have recreated bee syndrome using genetically engineered human cancer cells derived from fibrosarcoma. They found that without the enzymes needed to metabolize Mannose, cells replicated slowly and were more susceptible to chemotherapy.

In this latest study, the research team extracted human cancer cells from fibrosarcoma and knocked out their Mannose phosphate isomerase (MPI) gene, which is a genetically engineered human cancer cell that has difficulty metabolizing Mannose, thereby constructing a cell model of bee syndrome.

Massive Mannose influx beyond the metabolic capacity of these genetically engineered cancer cells induces metabolic remodeling, resulting in slow-cycling cells with limited deoxyribonucleoside triphosphates (dNTPs) .

Importantly, pharmacological inhibition of nascent dNTP biosynthesis was sufficient to delay cancer cell cycle progression, sensitize cancer cells to the chemotherapeutic drug cisplatin, and inhibit activation of dormant replication origins, suggesting that dNTP loss-induced genomic instability is a central mechanism for the anticancer activity of Mannose.

What is the anti-cancer mechanism of Mannose? A mechanistic model for the anticancer activity of Mannose in Mannose phosphate isomerase knockout (MPI-KO) human cancer cells

If we could find cancer types with lower activity of the enzyme that metabolizes Mannose, then Mannose could provide enough of a boost to make chemotherapy more effective.

The glycobiology of sugar metabolism in cancer cells is an underexplored frontier that may represent a treasure trove of potential treatments waiting to be discovered.

The most promising therapeutic use of Mannose so far is in the treatment of congenital disorders of glycation, which cause severe symptoms throughout the body, the research team said .

While Mannose may also deliver an extra hit to cancer cells, since Mannose occurs naturally throughout the body, it could improve cancer treatment without any unwanted side effects.

Paper link.