PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53.
Biochim Biophys Acta
; 1833(8): 1904-13, 2013 Aug.
Article
en En
| MEDLINE
| ID: mdl-23545415
ABSTRACT
PRIMA-1 is a chemical compound identified as a growth suppressor of tumor cells expressing mutant p53. We previously found that in the MDA-MB-231 cell line expressing high level of the mutant p53-R280K protein, PRIMA-1 induced p53 ubiquitination and degradation associated to cell death. In this study, we investigated the ability of PRIMA-1 to induce autophagy in cancer cells. In MDA-MB-231 and HCT116 cells, expressing mutant or wild type p53, respectively, autophagy occurred following exposure to PRIMA-1, as shown by acridine orange staining, anti-LC3 immunofluorescence and immunoblots, as well as by electron microscopy. Autophagy was triggered also in the derivative cell lines knocked-down for p53, although to a different extent than in the parental cells expressing mutant or wild type p53. In particular, while wild type p53 limited PRIMA-1 induced autophagy, mutant p53 conversely promoted autophagy, thus sustaining cell viability following PRIMA-1 treatment. Therefore, the autophagic potential of PRIMA-1, besides being cell context dependent, could be modulated in a different way by the presence of wild type or mutant p53. Furthermore, since both cell lines lacking p53 were more sensitive to the cytotoxic effect of PRIMA-1 than the parental ones, our findings suggest that a deregulated autophagy may favor cell death induced by this drug.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Autofagia
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Proteína p53 Supresora de Tumor
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Proteínas de la Membrana
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Mutación
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Neoplasias
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Proteínas del Tejido Nervioso
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Biochim Biophys Acta
Año:
2013
Tipo del documento:
Article
País de afiliación:
Italia