Biperiden and mepazine effectively inhibit MALT1 activity and tumor growth in pancreatic cancer.
Int J Cancer
; 146(6): 1618-1630, 2020 03 15.
Article
em En
| MEDLINE
| ID: mdl-31291468
ABSTRACT
MALT1 is a key mediator of NF-κB signaling and a main driver of B-cell lymphomas. Remarkably, MALT1 is expressed in the majority of pancreatic ductal adenocarcinomas (PDACs) as well, but absent from normal exocrine pancreatic tissue. Following, MALT1 shows off to be a specific target in cancer cells of PDAC without affecting regular pancreatic cells. Therefore, we studied the impact of pharmacological MALT1 inhibition in pancreatic cancer and showed promising effects on tumor progression. Mepazine (Mep), a phenothiazine derivative, is a known potent MALT1 inhibitor. Newly, we described that biperiden (Bip) is a potent MALT1 inhibitor with even less pharmacological side effects. Thus, Bip is a promising drug leading to reduced proliferation and increased apoptosis in PDAC cells in vitro and in vivo. By compromising MALT1 activity, nuclear translocation of c-Rel is prevented. c-Rel is critical for NF-κB-dependent inhibition of apoptosis. Hence, off-label use of Bip or Mep represents a promising new therapeutic approach to PDAC treatment. Regularly, the Anticholinergicum Bip is used to treat neurological side effects of Phenothiazines, like extrapyramidal symptoms.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Pancreáticas
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Fenotiazinas
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Biperideno
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Carcinoma Ductal Pancreático
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Proteína de Translocação 1 do Linfoma de Tecido Linfoide Associado à Mucosa
Tipo de estudo:
Clinical_trials
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Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Int J Cancer
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha