PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53.

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.

• Authors: Debora Russo, Laura Ottaggio, Giorgia Foggetti, Matilde Masini, Pellegrino Masiello, Gilberto Fronza, Paola Menichini
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1833 Issue 8 Pg. 1904-13 (Aug 2013) ISSN: 0006-3002 [Print] Netherlands
• PMID: 23545415 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Membrane Proteins
• Nerve Tissue Proteins
• PRIMA1 protein, human
• TP53 protein, human
• Tumor Suppressor Protein p53

Topics

• Autophagy (drug effects, genetics)
• Cell Line, Tumor
• Cell Survival (drug effects, genetics)
• HCT116 Cells
• Humans
• Membrane Proteins (pharmacology)
• Mutation
• Neoplasms (drug therapy, genetics, metabolism, pathology)
• Nerve Tissue Proteins (pharmacology)
• Tumor Suppressor Protein p53 (genetics, metabolism)