The Effects of Thiamine on Breast Cancer Cells

(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.

[1]  M Cascante,et al.  The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study. , 2001, European journal of biochemistry.

[2]  A. Vuylsteke,et al.  Faculty Opinions recommendation of Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study. , 2018, Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature.

[3]  M. V. Vander Heiden,et al.  Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. , 2011, Annual review of cell and developmental biology.

[4]  R. Trebukhina,et al.  Turnover of [14C]thiamin and activities of thiamin pyrophosphate-dependent enzymes in tissues of mice with Ehrlich ascites carcinoma. , 1984, Nutrition and cancer.

[5]  R. Trebukhina,et al.  Thiamine metabolism in the liver of mice with Ehrlich ascites carcinoma. , 1982, Neoplasma.

[6]  Dania Daye,et al.  Metabolic reprogramming in cancer: unraveling the role of glutamine in tumorigenesis. , 2012, Seminars in cell & developmental biology.

[7]  J. Lin,et al.  Elevated phosphorylation and activation of PDK-1/AKT pathway in human breast cancer , 2005, British Journal of Cancer.

[8]  C. Jordan,et al.  Metabolic Effects of Acute Thiamine Depletion Are Reversed by Rapamycin in Breast and Leukemia Cells , 2014, PLoS ONE.

[9]  P. Rubinstein HLA and IDDM: facts and speculations on the disease gene and its mode of inheritance. , 1991, Human immunology.

[10]  J. Bocchini,et al.  Thiamin deficiency: a possible major cause of some tumors? (review). , 2005, Oncology Report.

[11]  M. Tan,et al.  The Warburg effect in tumor progression: mitochondrial oxidative metabolism as an anti-metastasis mechanism. , 2015, Cancer letters.

[12]  R. Deberardinis,et al.  The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. , 2008, Cell metabolism.

[13]  A. Schulze,et al.  Targeting cancer metabolism--aiming at a tumour's sweet-spot. , 2012, Drug discovery today.

[14]  A. Harris,et al.  Pyruvate dehydrogenase and pyruvate dehydrogenase kinase expression in non small cell lung cancer and tumor-associated stroma. , 2005, Neoplasia.

[15]  J. Dumont,et al.  Metabolic reprogramming of the tumor , 2012, Oncogene.

[16]  A. Miller,et al.  Dietary intake of selected B vitamins in relation to risk of major cancers in women , 2008, British Journal of Cancer.

[17]  O. Frank,et al.  Elevated vitamin levels in colon adenocarcinoma as compared with metastatic liver adenocarcinoma from colon primary and normal adjacent tissue , 1981, Cancer.

[18]  W. Weber,et al.  Determination of thiamine in human plasma and its pharmacokinetics , 2004, European Journal of Clinical Pharmacology.

[19]  M. Yin,et al.  Oxidant Stress and B Vitamins Status in Patients With Non-Small Cell Lung Cancer , 2007, Nutrition and cancer.

[20]  P. Muti,et al.  Micronutrients Involved in One-Carbon Metabolism and Risk of Breast Cancer Subtypes , 2015, PloS one.

[21]  Jason Zastre,et al.  High-dose vitamin B1 reduces proliferation in cancer cell lines analogous to dichloroacetate , 2014, Cancer Chemotherapy and Pharmacology.

[22]  M. Donnino,et al.  Randomized, Double-Blind, Placebo-Controlled Trial of Thiamine as a Metabolic Resuscitator in Septic Shock: A Pilot Study , 2016, Critical care medicine.

[23]  A. Medline,et al.  Marginal dietary thiamin deficiency induces the formation of colonic aberrant crypt foci (ACF) in rats. , 2003, Cancer letters.

[24]  O. Warburg [Origin of cancer cells]. , 1956, Oncologia.