Investigation of the effects of vitamin D deficient and/or cholesterol-rich diets on intracellular energy metabolism during the neoplastic process in 4NQO-induced oral cancer rat models

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 promote carcinogenesis. Considering the vegetables and fruits as important sources for vitamins and dairy products as critical causes for high cholesterol in patients, we aimed at investigating the possible involvement of Vitamin D deficiency (VDD) and high cholesterol together in oral squamous cell carcinoma (OSCC) through modulating glycolysis. We initially compared total cholesterol, LDL, HDL, triglycerides, LDH, and Vitamin D levels of 23 OSCC patients and age and gender matched 30 control individuals and analyzed their correlation using Pearson's Analysis. Then, we used GEO datasets for gene set enrichment analysis. We used 4-nitroquinoline-1-oxide induced in vivo oral carcinogenesis models to investigate the contribution of VDD and high cholesterol during carcinogenesis via possible modulation of glycolysis. We, moreover, measured the cholesterol and gene expression levels in rat tongue tumor tissue samples using ELISA and qRT-PCR, respectively. We found that VDD and high cholesterol co-exist in OSCC patients and deregulation of cholesterol and Vitamin D levels results in enrichment of genes related to glycolysis. We, additionally, demonstrated that VDD and high cholesterol on their own and together led to formation of larger tumors in 4NQO induced in vivo cancer models, which is suppressed by glycolysis inhibition. In conclusion, we reported collaborative contribution of high cholesterol and VDD during oral carcinogenesis, which is mainly carried out via altering energy metabolism in tumor cells.