The Effects of Thiamine on Breast Cancer Cells

Molecules. 2018 Jun 16;23(6):1464. doi: 10.3390/molecules23061464.

Abstract

(1) Background: Thiamine is an important cofactor for multiple metabolic processes. Its role in cancer has been debated for years. Our aim is to determine if thiamine can convert the cellular metabolic state of breast cancer cells from anaerobic to aerobic, thus reducing their growth. (2) Methods: Breast cancer (MCF7) and non-tumorigenic (MCF10A) cell lines were treated with various doses of thiamine and assessed for changes in cell growth. The mechanism of this relationship was identified through the measurement of enzymatic activity and metabolic changes. (3) Results: A high dose of thiamine reduced cell proliferation in MCF7 (63% decrease, p < 0.0001), but didn’t affect apoptosis and the cell-cycle profile. Thiamine had a number of effects in MCF7; it (1) reduced extracellular lactate levels in growth media, (2) increased cellular pyruvate dehydrogenase (PDH) activities and the baseline and maximum cellular oxygen consumption rates, and (3) decreased non-glycolytic acidification, glycolysis, and glycolytic capacity. MCF10A cells preferred mitochondrial respiration instead of glycolysis. In contrast, MCF7 cells were more resistant to mitochondrial respiration, which may explain the inhibitory effect of thiamine on their proliferation. (4) Conclusions: The treatment of MCF7 breast cancer cells with 1 μg/mL and 2 μg/mL of thiamine for 24 h significantly reduced their proliferation. This reduction is associated with a reduction in glycolysis and activation of the PDH complex in breast cancer cells.

Keywords: aerobic glycolysis; aerobic metabolism; apoptosis; breast cancer; proliferation; thiamine.

MeSH terms

  • Anaerobiosis / drug effects
  • Breast Neoplasms / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Culture Media / chemistry
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Glycolysis / drug effects*
  • Humans
  • Lactic Acid / metabolism*
  • MCF-7 Cells
  • Pyruvate Dehydrogenase Complex / metabolism*
  • Thiamine / pharmacology*

Substances

  • Culture Media
  • Pyruvate Dehydrogenase Complex
  • Lactic Acid
  • Thiamine