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Abstract
Vitamin B1 (thiamine) is an essential water-soluble vitamin which is converted by Thiamine Pyrophosphokinase-1 to Thiamine pyrophosphate (TPP) which acts as a cofactor to activate enzymes in metabolic processes to generate ATP and nucleic acids. As Thiamine is not produced endogenously in the body, a regular dietary intake is essential. In cancer cells, there is an alteration of metabolic processes observed where the cells undergo anaerobic glycolysis even in the presence of oxygen, referred to as the Warburg effect, to produce ATP. The role of Thiamine dependent enzymes like Transketolase, -Ketoglutarate dehydrogenase and Pyruvate dehydrogenase, is critical in metabolism. Thus, we wanted to investigate the effect of low dose thiamine supplementation on thiamine dependent enzymes and eventually to determine their effect on cell proliferation. The ER+ve ductal breast carcinoma cell line, MCF-7 and Triple negative MDA MB 231 breast carcinoma cell line, were used and cells were treated with 10nM Thiamine media and with 3M Thiamine media to determine the dose effect. We also introduced these treatment groups to hypoxic environment to determine the effect of growth. We observed that there was an increase in the expression of thiamine dependent enzymes like TKT, KGDH and PDH 293 but not in the PDHe1 enzyme in both cancer cell lines. This high expression corresponded to an elevated activity of TKT and KGDH enzymes, however, we saw a decline in the PDH activity which supported the protein expression. The elevated cell number observed via different cell growth assays confirmed that thiamine supplementation at low doses did have a proliferative effect on both these cancer cell lines. Thus, we concluded that thiamine supplementation at low concentrations affected the enzyme expression which could indirectly affect cell proliferation in both cell lines, irrespective of the phenotypic differences.