Dimethylfumarate effectively inhibits lymphangiogenesis via p21 induction and G1 cell cycle arrest.
Exp Dermatol
; 25(3): 200-5, 2016 Mar.
Article
em En
| MEDLINE
| ID: mdl-26663097
ABSTRACT
Different pathologies, such as lymphoedema, cancer or psoriasis, are associated with abnormal lymphatic vessel formation. Therefore, influencing lymphangiogenesis is an interesting target. Recent evidence suggests that dimethylfumarate (DMF), an antipsoriatic agent, might have antitumorigenic and antilymphangiogenic properties. To prove this assumption, we performed proliferation and functional assays with primary human dermal lymphendothelial cells (DLEC). We could demonstrated that DMF suppresses DLEC proliferation and formation of capillary-like structures. Underlying apoptotic mechanisms could be ruled out. Cell cycle analysis demonstrated a pronounced G1-arrest. Further evaluations revealed increases in p21 expression. In addition, DMF suppressed Cyclin D1 and Cyclin A expression in a concentration-dependent manner. p21 knockdown experiments demonstrated a p21-dependent mechanism of regulation. Further analysis showed an increased p21 mRNA expression after DMF treatment. This transcriptional regulation was enforced by post-transcriptional and post-translational mechanisms. In addition, we could demonstrate that the combination of a proteasomal inhibitor and DMF superinduced the p21 expression. Hence, DMF is a new antilymphangiogenic compound and might be used in various illnesses associated with increased lymphangiogenesis.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Linfangiogênese
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Inibidor de Quinase Dependente de Ciclina p21
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Pontos de Checagem do Ciclo Celular
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Fumarato de Dimetilo
Limite:
Humans
Idioma:
En
Revista:
Exp Dermatol
Assunto da revista:
DERMATOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha