Systemically Administered D-allose Inhibits the Tumor Energy Pathway and Exerts Synergistic Effects With Radiation

Anticancer Res. 2024 May;44(5):1895-1903. doi: 10.21873/anticanres.16991.

Abstract

Background/aim: The present study investigated the anticancer effects of intraperitoneally administered D-allose in in vivo models of head and neck cancer cell lines.

Materials and methods: To assess the direct effects of D-allose, its dynamics in blood and tumor tissues were examined.

Results: D-allose was detected in blood and tumor tissues 10 min after its intraperitoneal administration and then gradually decreased. In vivo experiments revealed that radiation plus D-allose was more effective than either treatment alone. Thioredoxin-interacting protein (TXNIP) mRNA over-expression was detected after the addition of D-allose in in vitro and in vivo experiments. D-allose inhibited cell growth, which was associated with decreases in glycolysis and intracellular ATP levels and the prolonged activation of AMPK. The phosphorylation of p38-MAPK was also observed early after the administration of D-allose and was followed by the activation of AMPK and up-regulated expression of TXNIP in both in vitro and in vivo experiments.

Conclusion: Systemically administered D-allose appears to exert antitumor effects. Further studies are needed to clarify the appropriate dosage and timing of the administration of D-allose and its combination with other metabolic agents.

Keywords: AMPK; D-allose; TXNIP; glycolytic system; head and neck cancer.

MeSH terms

  • AMP-Activated Protein Kinases / metabolism
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Energy Metabolism / drug effects
  • Glucose* / metabolism
  • Glycolysis / drug effects
  • Head and Neck Neoplasms / drug therapy
  • Head and Neck Neoplasms / genetics
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / pathology
  • Head and Neck Neoplasms / radiotherapy
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Xenograft Model Antitumor Assays*

Substances

  • allose
  • Glucose
  • Carrier Proteins
  • TXNIP protein, human
  • AMP-Activated Protein Kinases