Thiamine mimetics sulbutiamine and benfotiamine as a nutraceutical approach to anticancer therapy.

@article{Jonus2020ThiamineMS,
  title={Thiamine mimetics sulbutiamine and benfotiamine as a nutraceutical approach to anticancer therapy.},
  author={Hunter C. Jonus and Charnel C Byrnes and Jaeah Kim and M. La Valle and Michael G. Bartlett and Hamid M Said and Jason Zastre},
  journal={Biomedicine \& pharmacotherapy = Biomedecine \& pharmacotherapie},
  year={2020},
  volume={121},
  pages={
          109648
        }
}
Malignant cells frequently demonstrate an oncogenic-driven reliance on glycolytic metabolism to support their highly proliferative nature. Overexpression of pyruvate dehydrogenase kinase (PDK) may promote this unique metabolic signature of tumor cells by inhibiting mitochondrial function. PDKs function to phosphorylate and inhibit pyruvate dehydrogenase (PDH) activity. Silencing of PDK expression has previously been shown to restore mitochondrial function and reduce tumor cell proliferation… Expand
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References

SHOWING 1-10 OF 51 REFERENCES
High-dose vitamin B1 reduces proliferation in cancer cell lines analogous to dichloroacetate
TLDR
The findings suggest that high-dose thiamine reduces cancer cell proliferation by a mechanism similar to that described for dichloroacetate. Expand
Paraptosis Cell Death Induction by the Thiamine Analog Benfotiamine in Leukemia Cells
TLDR
Evidence is presented that benfotiamine possess antitumor activity against leukemia cells and that this activity enhances the antiproliferative activities of cytarabine againstukemia cells, suggesting that ben fotamine has antitumors therapeutic potential. Expand
Dichloroacetate (DCA) as a potential metabolic-targeting therapy for cancer
TLDR
The generic drug dichloroacetate is an orally available small molecule that reverses the suppressed mitochondrial apoptosis in cancer and results in suppression of tumour growth in vitro and in vivo. Expand
The Effects of Thiamine on Breast Cancer Cells
TLDR
The treatment of MCF7 breast cancer cells with 1 μg/mL and 2 μg/ mL of thiamine for 24 h significantly reduced their proliferation, associated with a reduction in glycolysis and activation of the PDH complex in Breast cancer cells. Expand
Targeting Tumor Metabolism for Cancer Treatment: Is Pyruvate Dehydrogenase Kinases (PDKs) a Viable Anticancer Target?
TLDR
Inhibition of PDKs could be an attractive therapeutic approach for the development of anti-cancer drugs because of their role as regulator of PDC that catalyzes the oxidative decarboxylation of pyruvate in mitochondrion. Expand
Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives
TLDR
Benfotiamine, an S-acyl derivative practically insoluble in organic solvents, should be differentiated from truly lipid-soluble thiamine disulfide derivatives with a different mechanism of absorption and different pharmacological properties, which would explain why beneficial effects of benfutiamine have only been observed in peripheral tissues. Expand
Differential inhibition of PDKs by phenylbutyrate and enhancement of pyruvate dehydrogenase complex activity by combination with dichloroacetate
TLDR
It is shown both in cells and in mice that phenylbutyrate combined to DCA results in greater increase of PDHC activity compared to each drug alone, suggesting that therapeutic efficacy can be enhanced by combination of drugs increasing PDHC enzyme activity. Expand
The effect of thiamine supplementation on tumour proliferation. A metabolic control analysis study.
TLDR
Thiamine supplementation sufficient to correct existing thiamine deficiency stimulates tumour proliferation as predicted by MCA, and the tumour inhibitory effect at high doses of Thiamine is unexplained and merits further study. Expand
The adaptive regulation of thiamine pyrophosphokinase-1 facilitates malignant growth during supplemental thiamine conditions
TLDR
The findings suggest that the adaptive regulation of TPK1 may be an essential component in the cellular response to oxidative stress, and that during supplemental thiamine conditions its expression may be exploited by tumor cells for a redox advantage contributing to tumor progression. Expand
Pharmacologic doses of ascorbate act as a prooxidant and decrease growth of aggressive tumor xenografts in mice
TLDR
It is shown that ascorbate at pharmacologic concentrations was a prooxidant, generating hydrogen-peroxide-dependent cytotoxicity toward a variety of cancer cells in vitro without adversely affecting normal cells, and this action may have benefits in cancers with poor prognosis and limited therapeutic options. Expand
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