Antitumor effect of D-mannose on head and neck squamous cell carcinoma by inducing autophagy

Carbohydrates, especially glucose, are the essential source of energy for every cell. Studies have shown that mannose, a derivate of glucose, cannot be metabolized adequately in tumor cells, especially in combination with chemotherapeutic drugs. In contrast, healthy cells metabolize mannose as part of the glycogen synthesis.

This study was designed to systematically examine cytotoxicity, apoptosis and cell cycle alterations induced by mannose compared to glucose in HNSCC cell lines and non-malignant human bone marrow stem cells (MSC). The effect of different carbohydrates was investigated on HLaC78, FaDu cells and MSC in terms of dose dependency. Furthermore, the expression change of Glut1 and Glut3-transporters was examined, which are responsible for the cellular intake of glucose, in regard to mannose and glucose exposure, using the rt-PCR technique. In addition, transmission electron microscopy (TEM) was performed to detect autophagosomes as signs of autophagy.

The results showed a significant reduction in cell proliferation under 25 mM D-mannose compared to 25 mM D-glucose or standard conditions, while no alterations in cell viability could be observed. Higher concentrations of mannose caused cell death by necrosis. Cell cycle studies showed that significantly more cells switch to a resting phase under mannose compared to glucose. The expression of Glut1 and Glut3 receptors did not change under glucose or mannose exposure. TEM showed signs of increased formation of autophagosomes in tumor cells after mannose compared to glucose exposure. Cell proliferation of MSC was unaffected by the addition of mannose.

The current findings suggest that mannose may have a selective antitumor effect by induction of autophagy without interfering basic glucose uptake mechanisms.

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Publication History

Article published online:
10 June 2020