Linking vitamin B1 with cancer cell metabolism

Abstract

The resurgence of interest in cancer metabolism has linked alterations in the regulation and exploitation of metabolic pathways with an anabolic phenotype that increases biomass production for the replication of new daughter cells. To support the increase in the metabolic rate of cancer cells, a coordinated increase in the supply of nutrients, such as glucose and micronutrients functioning as enzyme cofactors is required. The majority of co-enzymes are water-soluble vitamins such as niacin, folic acid, pantothenic acid, pyridoxine, biotin, riboflavin and thiamine (Vitamin B1). Continuous dietary intake of these micronutrients is essential for maintaining normal health. How cancer cells adaptively regulate cellular homeostasis of cofactors and how they can regulate expression and function of metabolic enzymes in cancer is underappreciated. Exploitation of cofactor-dependent metabolic pathways with the advent of anti-folates highlights the potential vulnerabilities and importance of vitamins in cancer biology. Vitamin supplementation products are easily accessible and patients often perceive them as safe and beneficial without full knowledge of their effects. Thus, understanding the significance of enzyme cofactors in cancer cell metabolism will provide for important dietary strategies and new molecular targets to reduce disease progression. Recent studies have demonstrated the significance of thiamine-dependent enzymes in cancer cell metabolism. Therefore, this review discusses the current knowledge in the alterations in thiamine availability, homeostasis, and exploitation of thiamine-dependent pathways by cancer cells.

Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?

“…Thiamine (vitamin B1)-dependent enzymes (TDEs) linking glycolysis with the tricarboxylic acid cycle (TCA) pyruvate dehydrogenase (PDH), of the PPP transketolase (TKT), the TCA alpha-ketoglutarate deydrogenase (KGDH)/2-oxoglutarate deydrogenase (OGDH) complex, and the amino acid catabolism branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex are important enzymes for proliferative, anabolic, and survival purposes in tumor cells [11].…”

Utilidad clínica del lactato en el paciente oncológico

“…En el metabolismo aerobio, el piruvato es oxidado en Acetil coenzima A, la cual tiene múltiples propósitos en el ciclo de Krebs (acido cítrico); varios cofactores están envueltos en esta oxidación, incluyendo el pirofosfato de tiamina (PPT), sin el cual, no se genera Acetil CoA; si el piruvato no es usado para el ciclo de Krebs, este se convierte en lactato. Poco se ha estudiado al respecto, y se ha considerado pérdida de tiamina a través de la orina en pacientes con cáncer, así como una inhabilidad de activar al PPT; durante el crecimiento, las células de cáncer mantienen un nivel elevado de PPT, mientras que las células de huésped, exhiben un nivel muy bajo (Zastre et al, 2013), esta acumulación de tiamina en las células cancerosas, es la que conduce probablemente, a la alteración de tiamina en la malignidad (Dean et al, 2017).…”

Type B Lactic Acidosis Secondary to Thiamine Deficiency in a Child With Malignancy

“…Some studies suggest that rapidly growing malignant cells preferentially use thiamine, leading to a relative thiamine deficiency 8 and increased cancer proliferation. 9 Certain tumor cells overexpress glycolytic enzymes such as hexokinase, which may also help facilitate rapid proliferation.…”