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Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?

M Grimm1, B Calgéer2, P Teriete3

  • 1Department of Oral and Maxillofacial Surgery, University Hospital Tuebingen, Osianderstrasse 2-8, 72076, Tuebingen, Germany. dr.dr.martingrimm@googlemail.com.

Clinical & Translational Oncology : Official Publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
|July 17, 2015
PubMed
Abstract

Insights

This study found increased expression of thiamine-dependent enzymes (TDEs) in oral squamous cell carcinoma (OSCC). Targeting these enzymes may offer new therapeutic strategies for OSCC treatment.

Area of Science:

  • Biochemistry
  • Oncology
  • Metabolic pathways

Background:

  • Thiamine-dependent enzymes (TDEs) are critical for cellular metabolism, linking glycolysis, the TCA cycle, pentose phosphate pathway, and amino acid catabolism.
  • Their role in oral squamous cell carcinoma (OSCC) carcinogenesis and potential as therapeutic targets remain underexplored.

Purpose of the Study:

  • To investigate the expression of key TDEs, including pyruvate dehydrogenase (PDH), alpha-ketoglutarate dehydrogenase (KGDH/OGDH), and branched-chain alpha-ketoacid dehydrogenase (BCKDH), in OSCC development.
  • To assess the potential of targeting TDEs for novel metabolic therapies in OSCC.

Main Methods:

  • Immunohistochemistry and Western blot (WB) analysis were used to examine TDE expression.
  • Samples included normal oral mucosa, precursor lesions (hyperplasia, squamous intraepithelial neoplasia), and OSCC specimens.
  • OSCC tumor cell lines were utilized for WB analysis.

Main Results:

  • Pyruvate dehydrogenase (PDH) and KGDH (OGDH) showed significant overexpression in OSCC carcinogenesis compared to normal tissue, despite a decrease in total positive samples.
  • Branched-chain alpha-ketoacid dehydrogenase (BCKDH) was also significantly overexpressed during OSCC carcinogenesis.
  • Antibody specificity was confirmed via WB analysis.

Conclusions:

  • This study is the first to report increased TDE expression in OSCC.
  • Metabolic targeting of TDEs, potentially using compounds like oxythiamine, could sensitize OSCC cells to conventional therapies.
Keywords:
Oral squamous cell carcinomaOxybenfothiamineTargeted therapyThiamine-dependent enzymesTumor metabolism

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