Pyruvate dehydrogenase kinase expression and metabolic changes following dichloroacetate exposure in anoxic human colorectal cancer cells.
Exp Cell Res
; 331(1): 73-81, 2015 Feb 01.
Article
en En
| MEDLINE
| ID: mdl-25536473
ABSTRACT
Dichloroacetate (DCA) is a small molecule that inhibits pyruvate dehydrogenase kinase (PDK) to constrain the aerobic glycolytic pathway observed in many cancer cells and effectively kill them with limited cytotoxicity on normal cells. We previously showed that DCA induced a cytoprotective effect in different human colorectal cancer (CRC) cell lines under anoxic conditions. In this study, we investigated the molecular and metabolic changes that may be providing this cytoprotection. The expression profiles of PDK isoforms in SW480 and LS174T cells along with subsequent changes in pyruvate dehydrogenase (PDH) phosphorylation were assessed following DCA exposure. Changes in mitochondrial activity and subsequent glucose consumption and lactate production were then examined. We show evidence of differential regulation in PDH phosphorylation between different human CRC cells leading to differences in mitochondrial activity following DCA exposure. However, these effects did not lead to significant changes in cellular metabolism nor growth. In conclusion, DCA may only be beneficial in treating a subset of tumor types based on their molecular profiles of different PDK isoforms.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neoplasias Colorrectales
/
Proteínas Serina-Treonina Quinasas
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Ácido Dicloroacético
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Glucosa
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Hipoxia
Límite:
Humans
Idioma:
En
Revista:
Exp Cell Res
Año:
2015
Tipo del documento:
Article