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

17Citations
Citations of this article
17Readers
Mendeley users who have this article in their library.

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. © 2013 Elsevier B.V.

Cite

CITATION STYLE

APA

Russo, D., Ottaggio, L., Foggetti, G., Masini, M., Masiello, P., Fronza, G., & Menichini, P. (2013). PRIMA-1 induces autophagy in cancer cells carrying mutant or wild type p53. Biochimica et Biophysica Acta - Molecular Cell Research, 1833(8), 1904–1913. https://doi.org/10.1016/j.bbamcr.2013.03.020

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free