Targeting thiamine-dependent enzymes for metabolic therapies in oral squamous cell carcinoma?
Clin Transl Oncol
; 18(2): 196-205, 2016 Feb.
Article
em En
| MEDLINE
| ID: mdl-26179749
PURPOSE: Thiamine-dependent enzymes (TDEs) linking glycolysis with the tricarboxylic acid cycle (TCA) pyruvate dehydrogenase (PDH), of the pentose phosphate pathway transketolases (TKTs), the TCA alpha-ketoglutarate deydrogenase (KGDH)/2-oxoglutarate dehydrogenase (OGDH) complex, and the amino acid catabolism branched-chain alpha-ketoacid dehydrogenase (BCKDH) complex are crucial factors for tumor metabolism. The expression of these enzymes has not been analyzed for carcinogenesis of oral squamous cell carcinoma (OSCC) with special focus on new targeted metabolic therapies as yet. METHODS: TDEs PDH, KGDH (OGDH), and BCKDH were analyzed in normal oral mucosa (n = 14), oral precursor lesions (simple hyperplasia, n = 21; squamous intraepithelial neoplasia, SIN I-III, n = 35), and OSCC specimen (n = 46) by immunohistochemistry and western blot (WB) analysis in OSCC tumor cell lines. RESULTS: Although the total numbers of PDH and KGDH (OGDH) positive samples decreased in OSCC, both enzymes were significantly overexpressed in the carcinogenesis of OSCC compared with normal tissue. BCKDH has been demonstrated to be significantly overexpressed in the carcinogenesis of OSCC. Specificity of the antibodies was confirmed by WB analysis. CONCLUSIONS: This is the first study showing increased expression of TDEs in OSCC. Metabolic targeting of TDEs (including TKTs) by antagonistic compounds like oxythiamine or oxybenfothiamine may be a useful strategy to sensitize cancer cells to common OSCC cancer therapies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Complexo Piruvato Desidrogenase
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Tiamina
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Neoplasias Bucais
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Carcinoma de Células Escamosas
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3-Metil-2-Oxobutanoato Desidrogenase (Lipoamida)
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Complexo Cetoglutarato Desidrogenase
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Clin Transl Oncol
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha
País de publicação:
Itália