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.
Highlights
First described by Otto Warburg in 1956, it has long been known that that cancer cells favor anaerobic over aerobic metabolism to produce energy to fuel tumor growth
We determined whether supplementing media containing a baseline level of thiamine with increasing doses of thiamine hydrochloridedifferentially affected cellular proliferation in cancer and non-tumorigenic wild-type epithelial cells
After 24 h of thiamine treatment, we found that there was no significant difference in the progression of non-tumorigenic MCF10A cultures, using
Summary
First described by Otto Warburg in 1956, it has long been known that that cancer cells favor anaerobic over aerobic metabolism to produce energy to fuel tumor growth. Termed the Warburg effect, this effect appears to hold true whether or not oxygen is present, and can be termed aerobic glycolysis [1]. Overall, this metabolic shift causes cancer cells to have a higher rate of glucose metabolism, greater lactate production, and an enhanced biosynthesis of lipids and other macromolecules [1,2]. Thiamine acts as an effective gatekeeper of aerobic metabolism in its role as cofactor for pyruvate dehydrogenase, the enzyme that allows pyruvate to enter the Krebs cycle. A 2001 study by Comin-Anduix et al showed a biphasic effect of thiamine
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