Low vitamin D and high cholesterol facilitate oral carcinogenesis in 4NQO-induced rat models via regulating glycolysis

Oral Dis. 2023 Apr;29(3):978-989. doi: 10.1111/odi.14117. Epub 2022 Jan 28.

Abstract

Objectives: Diets and nutritional habits are critical during carcinogenic processes, where a diet poor in fruits and vegetables and rich in meat and other foods of animal origin facilitates carcinogenesis. In this study, we aimed at investigating the possible involvement of vitamin D deficiency (VDD) and high cholesterol (HC) together in oral squamous cell carcinoma (OSCC) through modulating glycolysis.

Subjects and methods: We compared total cholesterol, LDL, HDL, triglycerides, LDH, and vitamin D levels of OSCC patients and control individuals. We used GEO datasets for gene set enrichment and 4-nitroquinoline-1-oxide induced in vivo oral carcinogenesis models to investigate contribution of VDD and HC during carcinogenesis via possible modulation of glycolysis.

Results: We found that VDD and HC co-exist in OSCC patients, and deregulation of cholesterol and vitamin D levels results in enrichment of genes related to glycolysis. We, then, demonstrated that VDD and HC on their own and together facilitated the formation of larger tumors in 4NQO-induced in vivo cancer models, which are suppressed by glycolysis inhibition.

Conclusion: We reported collaborative contribution of HC and VDD during oral carcinogenesis, which is mainly carried out via altering energy metabolism in tumor cells.

Keywords: 4NQO; LDL; cholesterol; glycolysis; oral squamous cell carcinoma; vitamin D deficiency.

MeSH terms

  • Animals
  • Carcinogenesis / metabolism
  • Carcinoma, Squamous Cell* / chemically induced
  • Carcinoma, Squamous Cell* / genetics
  • Carcinoma, Squamous Cell* / metabolism
  • Glycolysis
  • Head and Neck Neoplasms*
  • Mouth Neoplasms* / genetics
  • Rats
  • Squamous Cell Carcinoma of Head and Neck
  • Vitamin D
  • Vitamin D Deficiency* / complications

Substances

  • Vitamin D